Cold Spring Harbor Symposia on Quantitative Biology

COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY

VOLUME XLII PART 1 COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY

VOLUME XLII

Chromatin

COLD SPRING HARBOR LABORATORY 1978 COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY VOLUME XLII

1978 by The Cold Spring Harbor Laboratory International Standard Book Number 0-87969-4)41-0 Library of Congress Catalog Card Number 34-8174

COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY Founded in 1933 by REGINALD G. HARRIS Director of the Biological Laboratory 1924 to 1936

Previous Symposia Volumes

I (1933) Surface Phenomena XXII (1957) Population Studies: Animal Ecology and Demography II (1934) Aspects of Growth XXIII (1958) Exchange of Genetic Material: Mechanism and Con- HI (1935) Photochemical Reactions sequences IV (1936) Excitation Phenomena XXIV (1959) Genetics and Twentieth Century Darwinism V (1937) Internal Secretions XXV (1960) BiologicalClocks VI (1938) Protein Chemistry XXVI (1961) Cellular Regulatory Mechanisms VII (1939) Biological Oxidations XXVII (1962) Basic Mechanisms in Animal Virus Biology VIII (1940) Permeability and the Nature of CoIl Membranes XXVHI (1963) Synthesis and Structure of Macromolecules IX (1941) Genes and Chromosomes: Structure and Organization XXIX (1964} Human Genetics X (1942) The Relation of Hormones to Development KXX (1965) Sensory Receptors XI (1946) Heredity and Variation in Microorganisms XXX[ (1966) The Genetic Code XII (1947) Nucleic Acids and Nucleoproteins XXXII (I967) Antibodies XIII (1948) Biological Applications of Tracer Elements XXX]]] (19f~) Replication of DNA in Microorganisms XIV (1949) Amino Acids and Proteins XXX]V (1969) The Mechanism of Protein Synthesis XV (1950) Origin and Evolution of Man XXXV (1970) Transcription of Genetic Material XVI (1951) Genes and Mutations XXXVI (1971) Structure and Function of Proteins at the Three- XVII (1952) The Neuron dimensional Level XVIII (1953) Viruses XXXVII (1972) The Mechanism of Muscle Contraction XIX (1954) The Mammalian Fetus: Physiological Aspects of De- XXXVIII (1973) Chromosome Structure and Function velopment XXXIX (1974) Tumor Viruses XX (1955) Population Genetics: The Nature and Causes of Genetic XL (1975) The Synapse Variability in Population XLI (1976) Origins of Lymphocyte Diversity XXI (1956) Genetic Mechanisms: Structure and Function

The Symposium Volumes are published by the Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, and may be purchased directly from the Laboratory or through booksellers. Symposium Participants

ADOLPH, KENNETH, Dept. of Biochemical Sciences, BIRD, ADRIAN, MRC Mammalian Genome Unit, Uni- Princeton University, New Jersey versity of Edinburgh, Scotland ALBERTS, BRUCE, Dept. of Biochemistry, University BIRNBOIM, H. C., Chalk River Nuclear Laboratory, of California, San Francisco Ontario, Canada AI~'AGEME, CANDIDO,Institute for Cancer Research, BIRNSTIEL, MAX, University of Zurich, Switzerland Fox Chase, Philadelphia, Pennsylvania BIRO, P. A., Dept. of Human Genetics, Yale Univer- ALLFREY, VINCENT, Rockefeller University, New sity, New Haven, Connecticut York, New York BlSWAS, D. K., Laboratory of Pharmacology, Har- ALONI, YOSEF, National Institutes of Health, Be- vard School of Dental Medicine, Boston, thesda, Maryland Massachusetts ALT, FREDERICK W., Dept. of Biological Sciences, BLACKBURN, ELIZABETH, Dept. of Biology, Yale Uni- Stanford University, Palo Alto, California versity, New Haven, Connecticut AMALRIC, F., Centre National de la Recherehe Scien- BLAKE, JUDITH, The Biological Laboratories, Har- tifique,Toulouse, France vard University, Cambridge, Massachusetts ARCECI, ROBERT J., Dept. of Biology, University of BLUMENFELD, MARTIN, Dept. of Genetics and Cell Rochester, New York Biology, University of Minnesota, St. Paul ARRIGO, PATRICK, Universit~ de Gen~ve, Switzerland BLUTHMANN, HORST, Max-Planck-lnstitut f'tirVirus- ASTRIN, SUSAN, Institute for Cancer Research, Fox forschung, Tubingen, Germany Chase, Philadelphia, Pennsylvania BONNER, JAMES, Division of Biology,California Insti- AXEL, RICHARD, Columbia University, New York, tute of Technology, Pasadena New York BONNER, INGELORE, Division of Biology, California BACHELER, LEE T., Tumor Virus Laboratory, Salk Institute of Technology, Pasadena Institute, San Diego, California BONNER, WILLIAM, NCI, National Institutes of BACHELLERIE, J. P., Centre National de la Recherche Health, Bethesda, Maryland Scientifique,Toulouse, France BOSWELL, ROBERT S., Dept. of Molecular, Cellular BAER, BRADFORD W., Dept. of Biological Chemistry, and Developmental Biology, University of Colo- Harvard Medical School, Boston, Massachusetts rado, Boulder BAILLIE, DAVID L., Dept. of Biological Sciences, Si- BINA-STEIN, MINOU, Dept. of HEW, National Insti- mon Fraser University, Burnaby, British Co- tutes of Health, Bethesda, Maryland lumbia, Canada BOURGEOIS, SUZANNE, Salk Institute, San Diego, BAK, A. LETH, Instituteof Medical Microbiology and California Human Genetics, University of Aarhus, Den- BOYER, HERBERT, Dept. of Biochemistry and Bio- mark physics, University of California,San Francisco BASERGA, RENATO, Dept. of Pathology, Temple Uni- BRACK, CH., Basel Institute for Immunology, versity, Philadelphia, Pennsylvania Switzerland BAUTZ, EKKEHARD K., Universi~t Heidelberg, Ger- BRADBURY, MORTON, Dept. of Physiology, Ports- many mouth Polytechnic, England BEDARD, DONNA L., Dept. of Biology, Johns Hopkins BRAM, STANLEY,Institut Pasteur, Paris, France University, Baltimore, Maryland BROKER, THOMASR., Cold Spring Harbor I~aboratory, BEER, MICHAEL, Dept. of Biophysics, Johns Hopkins New York University, Baltimore, Maryland BROWN, DONALDD., Dept. of Embryology, Carnegie BELLARD, MARIA, Institut de Chimie Biologique, Institution of Washington, Baltimore, Mary- Strasbourg, France land BENYAJATI, CHEEPTIP, Dept. of Biochemical Sciences, BRUNK, CLIFFORD, Biology Department, University Princeton University, New Jersey of California, Los Angeles BERNINGER, MARK, Dept. of Biology, Massachusetts BRUTLAG, DOUGLAS L., Dept. of Biochemistry, Stan- Institute of Technology, Cambridge ford University, California BEYER, ANN, Dept. of Molecular Biology, Vanderbilt BuscH, HARMS, Dept. of Pharmacology, Baylor Col- University, Nashville, Tennessee lege of Medicine, Houston, Texas BICK, MICHAEL D., Dept. of Cell Biology, Roche Insti- BUSTIN, MICHAEL, NIAMDD, National Institutes of tute, Nutley, New Jersey Health, Bethesda, Maryland BINGHAM, PAUL M., The Biological Laboratories, Bu2-r, TAUSEEF R., Dept. of Biochemistry, George- Harvard University,Cambridge, Massachusetts town University, Washington, D.C. vi SYMPOSIUM PARTICIPANTS

CAMERINI-OTERO, R. D., NIAMDD, National Insti- DARNELL, JAMES E., JR., Rockefeller University, tutes of Health, Bethesda Maryland New York, New York CANmDO, PETER, Dept. of Biochemistry, University DAVIDSON, ERIC H., Division of Biology, California of British Columbia, Vancouver, Canada Institute of Technology, Pasadena CANTOR, CHARLES S., Dept. of Chemistry, Columbia DAWID, IGOR, Carnegie Institution of Washington, University, New York, New York Baltimore, Maryland CAPLAN, ARNOLD I., Institut de Chimie Biologique, DEICH, ROBERT,Dept. of Biochemical Sciences, Frick Strasbourg, France Biochemistry Laboratory, Princeton University, CARLSON, MARIAN, Medical Center, Stanford Uni- New Jersey versity, California DE LORIMIER, The Biological Laboratories, Harvard CARROLL, DANA, Dept. of Microbiology, University University, Cambridge, Massachusetts of Utah, Salt Lake City DEPAMPHILIS,MELVIN L., Dept. of Biological Chemis- CARTER, CHARLESW., JR., Division of Health Affairs, try, Harvard Medical School, Boston, Mas- University of North Carolina, Chapel Hill sachusetts CASE, STEVEN T., Karolinska Institutet, Stockholm, DEVINE, EVELYN A., Dept. of Cell Biology, Roche In- Sweden stitute, Nutley, New Jersey CECIl, THOMAS R., Dept. of Biology, Massachusetts DIETERICH, ANN, Chemistry Dept. Columbia Univer- Institute of Technology, Cambridge sity, New York, New York CHALKLEY,ROGER, Dept. of Biochemistry, University DILAURO, MARXA PEPSICO, National Institutes of of Iowa, Iowa City Health, Bethesda, Maryland CHAMBON,PIERRE, Institut de Chimie Biologique, Fa- DIXON, GORDON, Division of Medical Biochemistry, culth de Md~decine, Strasbourg, France University of Calgary, Canada CHENG, SHEAU-MEI, Dept. of Biochemical Sciences, DONNECKE, DETLEF, Institut ftir Physiologische Che- Princeton University, New Jersey mie I, Phillipps Universi~t, Marburg, Germany CHOVNICK, ARTHUR,Biological Sciences Group, Uni- DREYER, CHRISTINE,Max-Planck-Institut Fdr Virus- versity of Connecticut, Storrs forschung, Tubingen, Germany CHow, LOUISE T., Cold Spring Harbor Laboratory, DUEE, S., Dept. of Biological Chemistry, Harvard New York Medical School, Boston, Massachusetts CHRISTENSEN, MARK, Dept. of Molecular Biology, DUNSMUIR, PAM, The Biological Laboratories, Har- Vanderbilt University, Nashville, Tennessee vard University, Cambridge, Massachusetts CHRISTIANSEN, GUNNA, Dept. of Biochemistry, Stan- DURICA,DAVID S., Dept. of Genetics and Cell Biology, ford University, California University of Connecticut, Storrs CHUNG, Su-YuN, Dept. of Biochemistry and Molecu- EDSTRSM, JAN-ERIK, Dept. of Histology, Karolinska lar Biology, Harvard University, Cambridge, Institutet, Stockholm, Sweden Massachusetts EFSTRATIADIS,ARGIRIS, The Biological Laboratories, CHURCH,CHARLF~ C., Dept. of Radiation Biology and Harvard University, Cambridge, Massachusetts Biophysics, University of Rochester, New York ELGIN, SARAH C. R., The Biological Laboratories, CLARK, STEPHEN H., Dept. of Genetics and Cell Biol- Harvard University, Cambridge, Massachusetts ogy, University of Connecticut, Storrs ERLANGER, BERNARD E., Dept. of Microbiology, Co- COHEN, LEONARDH., Institute for Cancer Research, lumbia University, New York, New York Fox Chase, Philadelphia, Pennsylvania ESMAILZADEH, ARDALAN K., Dept. of Biochemistry, COLE, DAVID R., Dept. of Biochemistry, University Johns Hopkins University, Baltimore, Mary- of California, Berkeley land CONNm'r, JuvrrH, Dept. of Microbiology and Immu- FARRON-FURSTENTHAL, FRANCIONE, Salk Institute, nology, Washington University, St. Louis, Mis- San Diego, California souri. FASY, THOMAS,Dept. of Cell Biology, Roche Institute, CREMISI, CHANTAL, Institut Pasteur, Paris, France Nutley, New Jersey CRICK, FRANCIS H. C., Salk Institute, San Diego, FEDORO~, NINA V., Carnegie Institution of Wash- California ington, Baltimore, Maryland CRIPPA, MARCO, Dept. de Biologie Animale, Univer- FEIGEI~ON, PHILLIP, Institute of Cancer Research, sith de Genbve, Switzerland Columbia University, New York, New York CROTHERS, DONALD M., Sterling Chemistry Labo- FELSENFELD, GARY, Public Health Service, National ratory, Yale University, New Haven, Con- Institutes of Health, Bethesda, Maryland necticut FINCH, JOHN, MRC Laboratory of Molecular Biology, CusIcK, MICHAEL, Dept. of Biological Chemistry, University Postgraduate Medical School, Cam- Harvard Medical School, Boston, Massachusetts bridge, England DAHMUS, MICHAEL, Dept. of Biochemistry, Univer- I~NNEGAN, DAVID, MRC Molecular Genetics Unit, sity of California, Davis University of Edinburgh, Scotland DANEHOLT, BERTIL, Dept. of Histology, Karolinska FLAVELL, R. A., Molecular Biology Laboratory, Uni- Instituter, Stockholm, Sweden versity of Amsterdam, The Netherlands SYMPOSIUM PARTICIPANTS vii

FLEISCHMAN, JULIAN B., Dept. of Microbiology and GRUOL, DONALD J., National Institutes of Health, Immunology, Washington University, St. Louis, Bethesda, Maryland Missouri HEARST, JOHN, Dept. of Chemistry, University of FLINT, JANE, Dept. of Biochemical Sciences, Prince- California, Berkeley ton University, New Jersey HEMMINKI, KARI, Mergenthaler Laboratory, Johns FOE, VICTORIA E., Dept. of Biochemistry and Bio- Hopkins University, Baltimore, Maryland physics, University of California Medical HERRICK, GLENN, Dept. of Molecular, Cellular and School, San Francisco Developmental Biology, University of Colorado, FRANKE, WERNER W., Institute of Experimental Pa- Boulder thology, German Cancer Research Center, HEUMANN, JOHN, Dept. of Molecular, Cellular and Neuenheimer, Germany Developmental Biology, University of Colorado, FREEDLENDER,ELIZABETH, University of North Caro- Boulder lina, Chapel Hill HILL, RONALDJ., CSIRO Genetics Research Labora- FREUND, ROBERT, Harvard University, Cambridge, tories, Epping, Australia Massachusetts HILLIKER, ARTHUR, Dept. of Genetics and Cell Biol- GALL, JOSEPH G., Dept. of Biology, Yale University, ogy, University of Connecticut, Storrs New Haven, Connecticut HIPSKIND, ROBERT, Dept. of Embryology, Carnegie GALLWrrZ, DImT~R, University of California, San Institution of Washington, Baltimore, Mary- Francisco land GARRARD,WILLIAM, Biochemistry Department, Uni- HONJO, TASUKU,Laboratory of Molecular Genetics, versity of Texas, Dallas NICHHD, National Institutes of Health, Be- GARREI~, JAMES I., Salk Institute, San Diego, thesda, Maryland California HSIANG, MYRTI.~.W., Dept. of Biochemistry, Univer- GEHRING, W. J., Abt. Zellbiologie, Universit~t Basel, sity of California, Berkeley Switzerland HSlEH, TAO-SHI, Dept. of Biochemistry, Stanford GERSH~.Y, EDWARD, Rockefeller University, New University, California York, New York HSIUNG, NANCY, Dept. of Biochemical Sciences, GEORGIEV, GEORGII P., Academy of Sciences of Frick Chemical Laboratory, Princeton, New USSR, Moscow Jersey GmnERT, WALTER, Dept. of Molecular Biology, Har- HUANG, P. C., Dept. of Biochemistry, Johns Hopkins vard University, Cambridge, Massachusetts University, Baltimore, Maryland GOLDBERG, Sm~, Rockefeller University, New York, HUANG, RUTH CHIH C., Mergenthaler Laboratory, New York Johns Hopkins University, Baltimore, Mary- GOLDKNOPF, IRA L., Texas Medical Center, Baylor land College of Medicine, Houston INGRAM, VERNON M., Dept. of Biology, Massachu- GO~HMIDT-CLERMONT, MICHEL, Dept. de Biolo- setts Institute of Technology, Cambridge gie Mol~culaire, Universit~ de Gen~ve, Switzer- ISENBERO, IRVIN, Dept. of Biochemistry and Bio- land physics, Oregon State University, Corvallis GOLDSMITH, ADA, National Cancer Institute Cytol- ISHIKAWA, KoNrrSUGU, Albert Einstein College of ogy Center, Melville, New York Medicine, Bronx, New York GOLVSMrrH, MERRILl., NIAMDD, National Institutes ISQUIERDO, MARTA, Rosenstiel Medical Research of Health, Bethesda, Maryland Center, Brandeis University, Waltham, Mas- GOLIrrHWArr, A., Dept. of Biochemistry, Case West- sachusetts ern Reserve University, Cleveland, Ohio JACKSON, VAUGHN, MRC Laboratory of Molecular GORDON, JOEL, Dept. of Anatomical Sciences, State Biology, University Postgraduate Medical University of New York, Stony Brook School, Cambridge, England GOROVSKY, MARTIN A., Dept. of Biology, University JAHN, CAROLYN, Walker Laboratory, Sloan-Ketter- of Rochester, New York ing Institute for Cancer Research, Rye, New GRAINGER, ROBERT M., Dept. of Biology, University York of Virginia, Charlottesville JAVAHERIAN,KASHI, Dept. of Cellular and Molecular GREEN, MELVIN, Dept. of Genetics, University of Biology, University of Tehran, Iran California, Davis JOLLY, DOUGLAS,Dept. of Biological Chemistry, Har- GRE~.NLEAF, ARNO, Dept. of Genetics and Cell Biol- vard Medical School, Boston, Massachusetts ogy, University of Connecticut, Storrs KAFATOS, FOTIS C., The Biological Laboratories, GRIFFITH, JACK, Dept. of Biochemistry, Stanford Harvard University, Cambridge, Massachu- University, California setts GROSS, R. H., Dept. of Biology, Johns Hopkins Uni- KAHANA, ZvI E., Dept. of Microbiology, Columbia versity, Baltimore, Maryland University, New York, New York GRUNSTEIN, MICHAEL, Molecular Biology Institute, KARP, ROBERT W., Dept. of Biochemistry, Stanford University of California, Los Angeles University, California viii SYMPOSIUM PARTICIPANTS

KARRER, KATHLEEN, Dept. of Zoology, Indiana Uni- LEWm, HERMAN, Cellular Biology Section, National versity, Bloomington Science Foundation, Washington D.C. KASAMATSU, HARUMI, Molecular Biology Institute, LI, HSUEH Jm, Division of Cell and Molecular Biol- University of California, Los Angeles ogy, State University of New York, Buffalo KELLER, WALTER, UniversitiitHeidelberg, Germany L,rroN, RICK, Dept. of Biochemistry, Stanford Uni- KEMP, DAVID J., Dept. of Biochemistry, Stanford versity, California University, California LILLY, D. M., G. D. Searle and Co., Ltd., High Wy- KHOURY, GEORGE, National Institutes of Health, combe, Bucks, England Bethesda, Maryland LINGREL, JERRY B., Dept. of Biological Chemistry, KOIDE, SAMUEL, Population Council, Rockefeller University of Cincinnati, Ohio University, New York, New York LISTOWSKY, IRVING, Albert Einstein College of Medi- KORNRERG, ROGER, Dept. of Biological Chemistry, cine, Bronx, New York Harvard Medical School, Boston, Massachusetts LITMAN, GARY, Walker Laboratory, Sloan-Kettering KOVACIC, R. T., The Biological Laboratories, Har- Institute for Cancer Research, Rye, New York vard University, Cambridge, Massachusetts LIZARm, PAUL, Rockefeller University, New York, Kuo, T[EN, Dept. of Biology, Systems Cancer Center, New York University of Texas, Houston LOHR, DENNm, Dept. of Biochemistry and Bio- KURTZ, DAVID, Biochemistry Dept., Columbia Uni- physics, Oregon State University, Corvallis versity, New York, New York Lu, PONZY, Dept. of Chemistry, University of Penn- LACY, EIJZABETH, Division of Biology, California In- sylvania, Philadelphia stitute of Technology, Pasadena Lusz, DONAL S., Biophysics Department, Johns Hop- LAEMMLX,ULRICH K., Dept. of Biochemical Sciences, kins University, Baltimore, Maryland Frick Chemical Laboratory, Princeton, New LtrrrER,LEONARD, MRC Laboratory of Molecular Bi- Jersey ology, University Postgraduate Medical School, LAMB, MARY,Dept. of Histology, Karolinska Institu- Cambridge, England tet, Stockholm, Sweden MACH, BERNARD, Dept. de Pathologie, Universit~ de LANGAN, THOMAS, Dept. of Pharmacology, Univer- Gen~ve, Switzerland sity of Colorado, Denver MAGEE, P. T., Yale University, New Haven, Con- LASKEY, R. A., MRC Laboratory of Molecular Biol- necticut ogy, University Postgraduate Medical School, MAIO, JOSEPH, Dept. of Cell Biology, Albert Einstein Cambridge, England College of Medicine, Bronx, New York LAg'r, SAMUEL, Genetics Division, Children's Hospi- MAIZELq, NANCY, Harvard University, Cambridge, tal, Boston, Massachusetts Massachusetts LAWN, RICHARD, Dept. of Molecular, Cellular and MANIATIS, THOMAS, Biology Division, California In- Developmental Biology, University of Colorado, stitute of Technology, Pasadena Boulder MANUELIDIS, LAURA, Dept. of Pathology, Yale Uni- LEDER, PHILIP, Public Health Service, National Insti- versity, New Haven, Connecticut tutes of Health, Bethesda, Maryland MARTIN, TERRANCE, Whitman Laboratory, Univer- LEE, C. S., Dept. of Zoology, University of Texas, sity of Chicago, Illinois Austin MARTINSON, HAROLDG., Dept. of Chemistry, Univer- LEER, JOHANN, Dept. of Molecular Biology, Univer- sity of California, Los Angeles sity of Aarhus, Denmark MARUSHmE,KEIJI, Laboratories for Reproductive Bi- LEFFAK, IRA M., Dept. of Biochemistry, Moffet Labo- ology, University of North Carolina, Chapel Hill ratory, Princeton University, New Jersey MAYFIELD,JOHN E., Dept. of Biological Sciences, Car- LEHRACH, HANS, Dept. of Biochemistry and Molecu- negie-Mellon University, Pittsburgh, Pennsyl- lar Biology, Harvard University, Cambridge, vania Massachusetts McCARTHY, BRIAN, Dept. of Biochemistry and Bio- LEPESANT, J. A., Yale University, New Haven, physics, University of California, San Francisco Connecticut McCoNNELL, DAVID, The Biological Laboratories, LERMAN, LEONARD, Dept. of Biological Sciences, Harvard University, Cambridge, Massachusetts State University of New York, Albany McGHEE, JAMES, NIAMDD, National Institutes of LESTOuROEON,WALLACE M., Dept. of Molecular Biol- Health, Bethesda, Maryland ogy, Vanderbilt University, Nashville, Ten- McKNIGHT, STEVEN L., Dept. of Biology, University nessee of Virginia, Charlottesville LEVINGER, LOUIS, Dept. of Biochemistry, University MEIJ~ZA, P~."rsR W., Sloan-Kettering Institute for of North Carolina, Chapel Hill Cancer Research, Rye, New York LEVY W., BEATEIZ, Dept. of Medical Biochemistry, MEREDITH, ROY D., Dept. of Microbiology, Columbia University of Calgary, Canada University, New York, New York LEWIN, BENJAMIN, MIT Press, Cambridge, Mas- MERTZ, JANET, McArdle Laboratory for Cancer Re- sachusetts search, University of Wisconsin, Madison SYMPOSIUM PARTICIPANTS ix

MILLER, DAVIDWAYNE, The Biological Laboratories, PALTER, KAREN, Dept. of Biochemistry and Bio- Harvard University, Cambridge, Massachusetts physics, University of California, San Fran- MILLER, OSCAR, Dept. of Biology, University of Vir- cisco ginia, Charlottesville PARDON, JOHN, Research Division, G. D. Searle and MIRAULT, MARC-EDOUARD, Dept. de Biologie Mol6cu- Co., Ltd., High Wycombe, Bucks, England laire, Universit6 de Gen~ve, Switzerland PARDUE, MARY IX)U, Massachusetts Institute of MIRZABEKOV, ANDREI, Academy of Sciences of USSR, Technology, Cambridge Moscow PARKER, CARL, Dept. of Biological Chemistry, Wash- MOERMAN, D. G., Dept. of Biological Sciences, Simon ington University, St. Louis, Missouri Frazer University, Burnaby, British Columbia, PATEL, GORDHAN L., Dept. of Zoology and Biochemis- Canada try, University of Georgia, Athens MORRIS, N. R., Dept. of Pharmacology, Rutgers Medi- PAUL, JOHN, Wolfson Laboratory for Molecular Pa- cal School, Piscataway, New Jersey thology, Beatson Institute for Cancer Research, MOUDmANAKIS, E. N., Mergenthaler Laboratory, Glasgow, Scotland Johns Hopkins University, Baltimore, Mary- PAULIN, D., Institut Pasteur, Paris, France land PAULSON, J., Biochemistry Sciences Dept., Princeton MULLINS, JAMES I., Dept. of Genetics and Cell Biol- University, New Jersey ogy, University of Minnesota, St. Paul PEACOCK, W. J., CSIRO, Division of Plant Industry, MusIcH, PmLHP, Dept. of Cell Biology, Albert Ein- Canberra City, Australia stein College of Medicine, Bronx, New York PELLICER, ANGEL, Columbia University, New York, MUSKAVITCH,MARC A., Dept. of Biochemistry, Stan- New York ford University, California PETES, THOMAS D., Massachusetts Institute of Tech- NARDL RONALD, Institute for Cancer Research, Fox nology, Cambridge Chase, Philadelphia, Pennsylvania PLAGENS, ULRICH, Laboratoire European de Biologie NATHANS, DANIEL, Dept. of Microbiology, Johns MoIAculaire, Heidelberg, Germany Hopkins University, Baltimore, Maryland POCCIA, D., Dept. of Biology, State University of New NELSON, LOUISE, Dept. of Histology, Karolinska In- York, Stony Brook stitutet, Stockholm, Sweden POLACOW, I., Dept. of Biochemistry, Albert Einstein NELSON, TIMOTHY, Dept. of Biochemistry, Stanford College of Medicine, Bronx, New York University, California PONDER, BRUCE, Mill Hill Laboratories, Imperial NEWBOLD, JOHN E., Dept. of Bacteriology and Immu- Cancer Research Fund, London, England nology, University of North Carolina, Chapel POTTER, STEVEN, Harvard Medical School, Boston, Hill Massachusetts NEWROCK, KENNETH, Institute for Cancer Research, POUPORE, STEVEN, Dept. of Molecular Biology, Van- Fox Chase, Philadelphia, Pennsylvania derbilt University, Nashville, Tennessee NOLL, MARKUS,Dept. of Cell Biology, University of PRENSKY, WOLF, Dept. of Molecular Cytology, Sloan- Basel, Switzerland Kettering Institute for Cancer Research, New O'DONNELL, JAmS E., University of Connecticut, York, New York Mansfield PRICZENIK, GEORGE, Rutgers University, New Bruns- ~O'FARRELL, PATRICK, Dept. of Biochemistry and wick, New Jersey Biophysics, University of California, San Fran- PRUNELL, ARIEL, Dept. of Biological Chemistry, Har- cisco vard Medical School, Boston, Massachusetts OLINS, ADA, Biology Division, Oak Ridge National RAE, PETER, Dept. of Biology, Yale University, New Laboratory, Tennessee Haven, Connecticut OLINS, DONALD, Biology Division, Oak Ridge Na- REEDER, RONALD, Dept. of Embryology, Carnegie tional Laboratory, Tennessee Institution of Washington, Baltimore, Mary- OLSON, MARK O. J., Dept. of Pharmacology, Baylor land College of Medicine, Houston, Texas REEVE, ANTHONY, Dept. of Biology, Johns Hopkins O'MALLEY, BERT, St. Lukes Episcopal Hospital, Bay- University, Baltimore, Maryland lor College of Medicine, Houston, Texas REEVES, RAYMOND, Dept. of Zoology, University of ORF, JOHN W., Dept. of Genetics and Cell Biology, British Columbia, Vancouver, Canada University of Minnesota, St. Paul RENZ, MANFRED, Max-Planck-lnstitut f'firVirusfor- OUDET, PIERRE, Institut de Chimie Biologique, schung, Tiibingen, Germany Faculth de M~decine, Strasbourg, France RmOLINI, ANN, The Biological Laboratories, Har- PAIGEN, KENNETH, Dept. of Health, Roswell Park vard University, Cambridge, Massachusetts Memorial Institute, Buffalo, New York RICHARDS, B. M., Research Division, G. D. Searle PALATNIK, CARL, Dept. offMicrobiology, University and Co., Ltd., High Wycombe, Bucks, England of Massachusetts, Worchester RILL, RANDOLPH L., Dept. of Chemistry, Institute of PALMITER, R., Dept. of Biochemistry, University of Molecular Biophysics, Florida State University, Washington, Seattle Tallahassee x SYMPOSIUM PARTICIPANTS

RODMAN, T., Cornell Medical College, New York, NIAMDD, National Institutes of" Health, Be- New York thesda, Maryland RODRIQUEZ, L. V., University of Texas, Houston S[NA, BARBARAJ., Dept. of Genetics and Cell Biology, ROEDER, ROBERT G., Dept. of Biological Chemistry, University of Minnesota, St. Paul Washington University, St. Louis, Missouri SINGER, DINAH, National Institutes of Health, ROSE, ANN, Dept. of Biological Sciences, Simon Bethesda, Maryland Frazer University, Burnaby, British Columbia, SMITH, MITCHELL, Mergenthaler Laboratory, Johns Canada Hopkins University, Baltimore, Maryland ROUW~.RE-YAN[V, JOSETTE, Institut Pasteur, Paris, SMULSON, MARK, Dept. of Biochemistry, Georgetown France University, Washington, D.C. RUBIN, GERRY M., Charles A. Dana Cancer Center, SOBELL, HENRY M., Dept. of Chemistry, University Sidney Farber Cancer Institute, Boston, Mas- of Rochester, New York sachusetts SOLLNER-WEBB, BARBARA, National Institutes of RUDERMAN, JOAN, Anatomy Dept., Harvard Medical Health, Bethesda, Maryland School, Boston, Massachusetts SPRADI.VNG, AU~N C., Dept. of Zoology, Indiana Uni- RUIz-CARILIX), ADOLFO, Max-Planck-lnstitut i~tir versity, Bloomington Molekulare Genetik, Berlin, Germany STEIN, ARNOLD, Dept. of HEW, National Institutes SABATINI, L., Dept. of Zoology, Indiana University, of Health, Bethesda, Maryland Bloomington STEIN, G. S., Dept. of Biochemistry, J. Hillis Miller SAHASRABUDDHE, C. G., Systems Cancer Center, De- Health Center, Gainsville,Florida velopmental Therapeutics, University of Texas, STEIN, JANET L., Dept. of Immunology and Medical Houston Microbiology, University of Florida, Gainesville SALSER, WINSTON, Center for Health Sciences, Uni- STEWART, BERNARD W., University of New South versity of California, Los Angeles Wales, Kensington, Australia SANDERS, MARILYN M., Dept. of Pharmacology, STOECKERT, CHRISTIAN, Dept. of Biophysics, Johns Rutgers Medical School, Piscataway, New Hopkins University, Baltimore, Maryland Jersey SuzuKI, YOSHIAKI, Dept. of Embryology, Carnegie SAUNDZRS, G. F., Systems Cancer Center, Develop- Institution of Washington, Baltimore, Mary- mental Therapeutics, University of Texas, land Houston SWIFT, HEWSON, Biology Dept., University of Chi- SCHAF~Z, KLAUSP., Universit~it Kons"tanz, Germany cago, Illinois SCHAFFHAUSEN, BRIAN, Dept. of Pathology, Harvard SZETO, WYNNE, Dept. of Biological Chemistry, Har- Medical School, Boston, Massachusetts vard Medical School, Boston, Massachusetts SCHMITZ, KZNNZTH S., Dept. of Chemistry, Univer- TAICHMAN, LORNE, Dept. of Oral Biology and Pathol- sity of Missouri, Kansas City ogy, State University of New York, Stony Brook SCHULTZ, LOREN, Yale University, New Haven, TATCHELL, KELLEY, Dept. of Biochemistry and Bio- Connecticut physics, Oregon State University, Corvallis SCHUTZ, GUNTHER, Dept. of Molecular Genetics, TEITELL, MURRAY F., Zoology Department, Univer- Max-Planck-Institut f'dr Molekulare Genetik, sity of Texas, Austin Berlin, Germany THIMMAPPAYA, BAYAR, Dept. of Human Genetics, SEALE, RONALD L., National Jewish Hospital and Yale University, New Haven, Connecticut Research Center, Denver, Colorado THOMAS, CHA~T.~-qA., Dept. of BiologicalChemistry, SEALY, LINDA, Biochemistry Dept., University of Harvard Medical School, Boston, Massachusetts Iowa, Iowa City THOMAS, JEAN O., Dept. of Biochemistry, University SEDAT, JOHN, Radiobiology Dept., Yale University, of Cambridge, England New Haven, Connecticut TISSI~RES, ALFRED, Dept. de Biologic Mol~culaire, SELmY, VERN, Cell Biochemistry Group, National Universith de Gen~ve, Switzerland Research Council of Canada, Ottawa TI.STY, THEA, Washington University, St. Louis, SHARP, PHILLIP, Dept. of Biology, Massachusetts In- Missouri stitute of Technology, Cambridge TOCCHINI-VAL~.NTINI, GLAUCO, Laboratory of Cell SHAW, BARBARARAMSAY, Dept. of Chemistry, Duke Biology, Consiglio Nazionale delle Ricerche, University, Durham, North Carolina Rome, Italy SHAW, PHYLLIS, Systems Cancer Center, Develop- TONEGAWA, SUSUMU, Basel Institute for Immunol- mental Therapeutics, University of Texas, ogy, Switzerland Houston TOWLE, HOWARD, Dept. of Medicine, University of SmVER, LEE M., The Biological Laboratories, Har- Minnesota, Minneapolis vard University, Cambridge, Massachusetts TRUMBORE, C. N., Dept. of Chemistry, University of SIM, GEK KEE, Division of Biology, California Insti- Delaware, Newark tute of Technology, Pasadena TSAI, MINC,-JER, Dept. of Cell Biology,Baylor College SIMPSON, ROBERT T., Developmental Biochemistry, of Medicine, Houston, Texas SYMPOSIUM PARTICIPANTS xi

TSAI, SOPHIA, Dept. of Cell Biology, Baylor College WOLFNER, MARIANA F., Dept. of Biochemistry, Stan- of Medicine, Houston, Texas ford University, California T~AN, DOROTHY, Children's Hospital, Boston, Mas- WOIL~EMUTH-KARASHOW, DEBRA J., Dept. of Human sachusetts Genetics and Development, Columbia VARSHAVSKY, ALEXANDER J., Academy of Sciences WOLLACK, JAN B., Columbia University, New York, of USSR, Moscow New York VIDALI, GEORGIO, Dept. of Cell Biology, Rockefeller WOODCOCK, C. L. F., Dept. of Zoology, University University, New York, New York of Massachusetts, Amherst WAGNER, ROBERT P., Dept. of Zoology, University WooLEY, JOHN C., Harvard University, Cambridge, of Texas, Austin Massachusetts WAHN, HARVEY L., Carnegie Institutionof Washing- WORCEL, ABE, Dept. of Biochemical Sciences, Frick ton, Baltimore, Maryland Chemical Laboratory, Princeton University, WALKER, BARBARA,Dept. of Molecular Biology, Van- New Jersey derbilt University, Nashville, Tennessee WRAY, WAYNE, Dept. of Cell Biology, Baylor College WAI~H, DONAL A., Dept. of Biological Chemistry, of Medicine, Houston, Texas University of California, Davis Wu, B., Harvard University, Cambridge, Massa- WASSARMAN, PAUL M., Dept. of Biological Chemis- chusetts try, Harvard Medical School, Boston, Massa- Wu, CARL, Harvard University, Cambridge, Mas- chusetts sachusetts WEINBERG, ERIC, Mergenthaler Laboratory, Johns Wu, JUNG-RUNG, CaliforniaInstitute of Technology, Hopkins University, Baltimore, Maryland Pasadena WEINSTOCK, RUTH, Columbia University, New York, YAMAMOTO, KEITH, Biochemistry Department, Uni- New York versity of California, San Francisco WEINTRAUB, HAROLD, Dept. of Biochemical Sciences, YAMAZAKI, SUNAO, National Institutes of Health, Frick Chemical Laboratory, Princeton Univer- Bethesda, Maryland sity, New Jersey YANIV, MOSHE, Institut Pasteur, Paris, France WEISSMAN, SHERMAN M., Dept. of Human Ge- YAO, MENG-CHAO, Dept. of Biology, Yale University, netics, Yale University, New Haven, Connecti- New Haven, Connecticut cut Yu, L. C., Dept. of Molecular Cytology, Sloan-Ketter- WEISSMANN, CHARLES, Institute for Molecular Biol- ing Institute for Cancer Research, New York, ogy, University of Zurich, Switzerland New York WENSINK, PIlfER, Rosenstiel Basic Medical Sciences ZACHAU, H. G., Institut Rir Physiologische Chemie, Research Center, Brandeis University, Wal- Universitiit Munchen, Germany tham, Massachusetts ZALTA, J. P., Centre National de la Recherche Scien- WESTMORELAND, BARBARA, Dept. of BiologicalChem- tifique,Toulouse, France istry, Harvard Medical School, Boston, Mas- ZASLOFF, MICHAEL, NIAMDD, National Institutesof sachusetts Health, Bethesda, Maryland WF_.STPHAL, HENRY, Laboratory of Molecular Genet- ZIMMER, STEVEN, UniversitiitBasel, Switzerland ics, National Institutes of Health, Bethesda, ZOLAN, MIRIAM, Columbia University, New York, Maryland New York WILLIAMSON, PATRICK, NIAMDD, National Insti- ZUCKERKANDLE, EMILE, Marine Biological Labora- tutes of Health, Bethesda, Maryland tory, Woods Hole, Massachusetts First row: H. G. Zachau/W. Wray/E. Freedlender Second row: J. Pardon, J. Finch/E. K. Bautz Third row: A. Mirzabekov/P. Chambon, M. Noll, F. Crick First row: M. Bradbury/W. Keller/R. Chalkley/L. Lutter Sec<~nd row: H. Weintraub/A. Worcel, A. Olins Third row: C. A. Thomas, W. Gilbert/Y. Aloni First row: J. Hearst/V. M. Ingram/Blackford lawn Second row: K. Paigen/H. Lewis/D. R. Cole/O. Miller Third row: Lunch break/G. Felsenfeld, A. Tissi~res Fourth row: D. Olins/M. Botchan, J. D. Watson First row: M. Bradbury/W. Keller/R. Chalkley/L. Lutter Sec<~nd row: H. Weintraub/A. Worcel, A. Olins Third row: C. A. Thomas, W. Gilbert/Y. Aloni First row: J. Hearst/V. M. Ingram/Blackford lawn Second row: K. Paigen/H. Lewis/D. R. Cole/O. Miller Third row: Lunch break/G. Felsenfeld, A. Tissi~res Fourth row: D. Olins/M. Botchan, J. D. Watson Foreword

The chromosome has long been one of the main research thrusts at Cold Spring Harbor, and numerous of our Symposia have asked as to its structure. The decision to choose it again for this year's meeting reflects the amazing progress made over the last three years on the chromosomal DNA-protein complexes that today everyone calls chromatin. Here the key discovery has been the finding that it has a repeating subunit (the nucleosome) comprised of some two hundred base pairs wrapped around an octamer of histones. With this fact to work from, the chromatin field has broken out of the speculative straightjacket that so long held it down and has emerged as one of the most exciting areas in biology. So we anticipated a full meeting where we would learn many new facts we would want to remember. The final product, however, was more exciting than anyone could have hoped. The existence of recombinant DNA and the powerful new DNA sequencing methods have begun to generate results that a few years ago we would have predicted could not emerge until a decade or two of more sustained work. Even more surprisingly, a variety of experimental approaches gave us the bombshell that functional RNA molecules can derive from physically quite separate sections along a DNA molecule. At the end we were both overwhelmed and dazzled, and many participants left feeling they had been part of an historic occasion. The great breadth of the prospective program meant that Mike Botchan and I had to seek much outside help. Invaluable advice was given by Drs. Bruce Alberts, Pierre Chambon, Francis Crick, Gerry Felsenfeld, Joe Gall, Aaron Klug, Roger Kornberg, Mary Lou Pardue, and Harold Weintraub. A total of one hundred and eight formal presentations were given at the week-long gathering, which started the evening of June 1 and continued to the morning of June 8. Three hundred and seventy-five participants were in attendance, a Symposium record. Only with the receipt of substantial outside financial help could we have invited so many speakers. Again we are most indebted to the National Institutes of Health, the National Science Foundation, and the United States Energy Research and Develop- ment Administration. Emergence of the resulting Symposium volume has required much devoted work by our Publications Department, and we are most indebted to its Director, Nancy Ford, who has been ably assisted by Annette Zaninovic, Roberta Salant, and Thelma Sambrook. The organization of the Symposium itself was also a major task and here much credit must be given to Gladys Kist and Joan Carpenter. Without their cheerful compe- tence we would not have been able to give so many visitors the gracious attention which has long been a mark of the Symposium week.

J. D. Watson

xv Contents

Part 1

Symposium Participants

Foreword XV

Nucleosome Structure I: Crystallographic Analysis X-ray and Electron Microscope Analyses of Crystals of Nucleosome Cores J. T. Finch and A. Klug 1 Scattering Studies of Chromatin Subunits J. F. Pardon, R. I. Cotter, D. M. J. Lilley, D. L. Worcester, A. M. Campbell, J. C. Wooley, and B. M. Richards 11 DNA Structure in Chromatin and in Solution Studied by Electron Microscopy and Neutron and X-ray Scattering S. Brain, S. Kouprach, and P. Baudy 23

Nucleosome Structure II: Conformational Studies Conformational States of Chromatin M. Zama, P. N. Bryan, P. E. Harrington, A. L. Olins, and D. E. Olins 31 Ultrastructure of Chromatin Subunits during Unfolding, Histone Depletion, and Reconstruction C. L. F. Woodcock and L.-L. Y. Frado 43 Nucleosome Structure, DNA Folding, and Gene Activity R. D. Camerini- Otero, B. Sollner-Webb, R. H. Simon, P, Williamson, M. Zasloff, and G. Felsenfeld 57 Internal Structure of the Nucleosome: DNA Folding in the Conserved 140-Base- pair Core Particle M. Noll 77 Conformational Flexibility in DNA Structure as Revealed by Structural Studies of Drug Intercalation and Its Broader Implications in Understanding the Organization of DNA in Chromatin H. M. Sobell, B. S. Reddy, K. K. Bhan- dary, S. C. Jain, T D. Sakore, and T P. Seshadri 87 Relation of Nucleosomes to DNA Sequences A. Prunell and R. D. Kornberg 103 Domains in Chromatin Structure T. Igd-Kemenes and H. G. Zachau 109

Nucleosome Structure III: The Core The Nucleosome Core Protein J. 0. Thomas and P. J. C. Butler 119 Histone-DNA Interactions in Chromatin Core Particles R. T. Simpson, J. P. Whitlock, Jr., M. Bina-Stein, and A. Stein 127 Characterization of DNase-I Cleavage Sites in the Nucleosome L. C. Lutter 137 The Structure of Nucleosomes: The Arrangement of Histones in the DNA Grooves and Along the DNA Chain A. D. Mirzabekov, V. V. Shick, A. V. Belyavsky, V. L. Karpov, and S. G. Bavykin 149 Evolutionary Conservation of Histone-Histone Binding Sites: Evidence from In- terkingdom Complex Formation S. Spiker and I. Isenberg 157 Nucleohistone Assembly: Sequential Binding of Histone H3-H4 Tetramer and Histone H2A-H2B Dimer to DNA A. Ruiz-Carrillo and J. L. Jorcano 165 Chromatin Assembly and Transcription in Eggs and Oocytes of Xenopus laevis R. A. Lasky, B. M. Honda, A. D. Mills, N. R. Morris, A. H. Wyllie, J. E. Mertz, E. M. De Robertis, and J. B. Gurdon 171 Chromatin Structures of Main-band and Satellite DNAs in Drosophila melanogaster Nuclei as Probed by Photochemical Cross-linking of DNA with Trioxsalen C.-K. J. Shen and J. E. Hearst 179 xvii xviii CONTENTS

Chromatin Structure in Living Cells T R. Cech, D. Potter, and M. L. Pardue 191 Dynamics of Nucleosome Structure Studied by Fluorescence A. E. Dieterich, R. Axel, and C R. Cantor 199 Electric Dichroism Studies of the Size and Shape of Nucleosomal Particles L. Klevan, M. Hogan, N. Dattagupta, and D. M. Crothers 207

Nucleosome Structure IV: H1 Interactions

The Multifunctional Role of Histone H1, Probed with the SV40 Mini- chromosome J.D. Griffith and G. Christiansen 215 Biochemical and Ultrastructural Analysis of SV40 Chromatin W. Keller, U. Miiller, I. Eicken, I. Wendel, and H. Zentgraf 227 Histone H1 Involvement in the Structure of the Chromosome Fiber M. Renz, P. Nehls, and J. Hozier 245 H1 Histone and the Condensation of Chromatin and DNA R.D. Cole, G. M. Lawson, and M. W. Hsiang 253 The Role of H1 in the Structure of Chromatin J. Gaubatz, R. Hardison, J. Murphy, M. E. Eichner, and R. Chalkley 265 Satellite DNA, H1 Histone, and Heterochromatin in Drosophila virilis M. Blu- menfeld, J. W. Orf, B. J. Sina, R. A. Kreber, M. A. Callahan, and L. A. Snyder 273 Nucleosomes, Histone Interactions, and the Role of Histones H3 and H4 E. M. Bradbury, T Moss, H. Hayashi, R. P. Hjelm, P. Suau, R. M. Stephens, J. P. Baldwin, and C. Crane-Robinson 277 Nucleosome Structure I: All Four Histones, H2A, H2B, H3, and H4, Are Required to Form a Nucleosome, but an H3-H4 Subnucleosomal Particle Is Formed with H3-H4 Alone P. Oudet, J. E. Germond, M. Sures, D. Gallwitz, M. Bel- lard, and P. Chambon 287 Nucleosome Structure II: Structure of the SV40 Minichromosome and Electron Microscopic Evidence for Reversible Transitions of the Nucleosome Struc- ture P. Oudet, C. Spadafora, and P. Chambon 301

Chromosome Coiling and Assembly

Molecular Architecture of the Chromatin Fiber A. Worcel 313 v Bodies Are Close-packed in Chromatin Fibers A.L. Olins 325 A Direct Approach to the Structure of Eukaryotic Chromosomes J. Sedat and L. Manuelidis 331 Metaphase Chromosome Structure: The Role of Nonhistone Proteins U.K. Laemmli, S. M. Cheng, K. W. Adolph, J. R. Paulson, J. A. Brown, and W.. R. Baumbach 351 Metaphase Chromosome Architecture W. Wray, M. Mace, Jr., V. Daskal, and E. Stubblefield 361 Higher-order Structure of Mitotic Chromosomes A. Leth Bak and J. Zeuthen 367 Immunological Probes for Chromatin Structure M. Bustin, P. D. Kurth, E. N. Moudrianakis, D. Goldblatt, R. Sperling, and W. B. Rizzo 379 Functional Organization of Polytene Chromosomes M. Jamrich, A. L. Greenleaf, F A. Bautz, and E. K. F Bautz 389 Immunochemical Studies on the 5-Methylcytosine Content of African Green Mon- key Satellite DNA Z. E. Kahana, 0. J. Miller, and B. F. Erlanger 397 The Generation and Propagation of Variegated Chromosome Structures H. Weintraub, S. J. Flint, I. M. Leffak, M. Groudine, and R. M. Grainger 401 Assembly of SV40 and Polyoma Minichromosomes during Replication C. Crd- misi, A. Chestier, and M. Yaniv 4O9 Segregation of Some Chromosomal Proteins during Cell Replication E. F. Freed- lender, L. Taichrnan, and O. Smithies 417 Histone Changes during Chromatin Remodeling in Embryogenesis K. M. New- rock, C. R. Alfageme, R. V. Nardi, and L. H. Cohen 421 Persistence of Nucleosomes on DNA during Chromatin Replication R. L. Seale 433 CONTENTS xm

Simple Systems

Localization of the HU Protein on the Escherichia coli Nucleoid J. Rouvi~re- Yaniv 439 The Structure of Genes, Intergenic Sequences, and mRNA from SV40 Virus B. Thimmappaya, V. B. Reddy, R. Dhar, M. Celma, K. N. Subramanian, B. S. Zain, J. Pan, and S. M. Weissman 449 On the Structure of Eukaryotic, Prokaryotic, and Viral Chromatin A.J. Var- shavsky, V. V. Bakayev, S. A. Nedospasov, and G. P. Georgiev 457 Histone Organization in Chromatin: Comparisons of Nucleosomes and Subnucleo- somal Particles from Erythrocyte, Myeloma, and Yeast Chromatin R.L. Rill and D. A. Nelson 475 The Gene-size DNA Molecules in Oxytricha R. M. Lawn, J. M. Heumann, G. Herrick, and D. M. Prescott 483 Histones and Chromatin Structure in Tetrahymena Macro- and Micronuclei M. A. Gorovsky, C. Glover, C. A. Johmann, J. B. Keevert, D. J. Mathis, and M. Samuelson 493 Structural Organization and Control of the Ribosomal Genes in Physarum V. G. Allfrey, E. M. Johnson, Z Y.-C. Sun, V. C. Littau, H. R. Matthews, and E. M. Bradbury 505

Transcription I: Primary Products The Definition of Transcription Units for mRNA J. E. Darnell, R. Evans, N. Fraser, S. Goldberg, J. Nevins, M. Salditt-Georgieff, H. Schwartz, J. Weber, and E. Ziff 515 Spliced Segments at the 5' Termini of Adenovirus-2 Late mRNA: A Role for Heterogeneous Nuclear RNA in Mammalian Cells S.M. Berget, A. J. Berk, T. Harrison, and P. A. Sharp 523 Adenovirus-2 Messengers-An Example of Baroque Molecular Architecture T R. Broker, L. T Chow, A. R. Dunn, R. E. Gelinas, J. A. Hassell, 1). F. Klessig,J. B. Lewis, R. J. Roberts, and B. S. Zain 531 Displacement Loops in Adenovirus DNA-RNA Hybrids H. Westphal and S.-P. Lai 555 Splicing ofSV40 mRNAs: A Novel Mechanism for the Regulation of Gene Expres- sion in Animal Cells Y. Aloni, S. Bratosin, R. Dhar, O. Laub, M. Horowitz, and G. Khoury 559 A Novel Sequence Arrangement of SV40 Late RNA M.-T Hsu and J. Ford 571 Faithful Gene Transcription by Eukaryotic RNA Polymerases in Reconstructed Systems C. S. Parker, J. A. Jaehning, and R. G. Roeder 577 Studies on Gene Transcription In Vitro by Analysis of the Primary Tran- scripts R. C. C. Huang, M. M. Smith, and A. E. Reeve 589 Properties of Transcriptionally Active Chromatin J. Paul, E. J. Zollner, R. S. Gilmour, and G. D. Birnie 597

Part 2

Transcription II: Regulated Systems Regulation of Gene Expression in Chick Oviduct B. W. O'Malley, M.-J. Tsai, S. Y. Tsai, and H. C. Towle 605 Hormonal Control of Egg White Protein Messenger RNA Synthesis in the Chicken Oviduct G. Schlitz, M. C. Nguyen-Huu, K. Giesecke, N. E. Hynes, B. Groner, T Wurtz, and A. E. Sippel 617 Mammary Tumor Virus DNA: A Glucocorticoid-responsive Transposable Ele- ment K. R. Yamamoto, M. R. Stallcup, J. Ring, and G. M. Ringold 625 xx CONTENTS

Regulation of Gene Expression in the Chick Oviduct by Steroid Hormones R. D. Palmiter, E. R. Mulvihill, G. S. McKnight, and A. W. Senear 639 Amplification of Folate Reductase Genes in Methotrexate-resistant Cultured Mouse Cells R. T.. Schirnke, F. W. Alt, R. E. Kellems, R. Kaufman, and J. B. Bertino 649 Hormonal Modulation of ~ 2u Globulin mRNA: Sequence Measurements Using a Specific cDNA Probe P. Feigelson and D. T Kurtz 659 The Nucleolus, a Model for Analysis of Chromatin Controls H. Busch, N. R. Ballal, R. K. Busch, Y. C. Choi, F. Davis, I. L. Goldknopf S.-I. Matsui, M. S. Rao, and L. I. Rothblum 665 Stimulation of Ribosomal RNA Synthesis in Isolated Nuclei and Nucleoli by Partially Purified Preparations of SV40 T Antigen R. Baserga, T. Ide, and S. Whelly 685 Purification of a Protein from Unfertilized Eggs of Drosophila with Specific Affin- ity for a Defined DNA Sequence and the Cloning of This DNA Sequence in Bacterial Plasmids H. Weideli, P. Sehedl, S. Artivanis-Tsakonas, R. Steward, R. Yuan, and W. J. Gehring 693

Transcriptionally Active Chromatin

The Structure of the Transcriptionally Active Ovalbumin Genes in Chroma- tin A. Garel and R. Axel 701 Structure of Xenopus Ribosomal Gene Chromatin during Changes in Genomic Transcription Rates R. Reeves 709 Modulation of Ribosomal RNA Synthesis in Oncopeltus fasciatus: An electron Microscopic Study of the Relationship between Changes in Chromatin Struc- ture and Transcriptional Activity V.E. Foe 723 Electron Microscopic Analysis of Chromosome Metabolism in the Drosophila melanogaster Embryo S. L. McKnight, M. Bustin, and O. L. Miller, Jr. 741 Morphology of Transcriptionally Active Chromatin W. W Franke, U. Scheer, M. Trendelenburg, H. Zentgraf, and H. Spring 755 Structure of rDNA-containing Chromatin of Tetrahymena pyriformis Analyzed by Nuclease Digestion Do J. Mathis and M. A. Gorovsky 773 Nucleosome Structure III: The Structure and Transcriptional Activity of the Chromatin Containing the Ovalbumin and Globin Genes in Chick Oviduct Nuclei M. Bellard, t7. Gannon, and P. Charnbon 779 Structure and Function of the Low-salt Extractable Chromosomal Proteins. Pref- erential Association of Trout Testis Proteins H6 and HMG-T with Chromatin Regions Selectively Sensitive to Nucleases B. Levy W., N. C. W Wong, D. C. Watson, E. H. Peters, and G. H. Dixon 793 Transcription of Polytene Chromosomes and of the Mitochondrial Genome in Drosophila melanogaster J. J. Bonner, M. Berninger, and M. L. Pardue 803 Modified Histones in HeLa and Friend Erythroleukemia Cells Treated with n- Butyrate M. G. Riggs, R. G. Whittaker, J. R. Neumann, and V. M. Ingram 815 The Effect of Heat Shock on Gene Expression in Drosophila melanogaster M.-E. Mirault, M. Goldschmidt-Clermont, L. Moran, A. P. Arrigo, and A. Tissi~res 819 Correlation of Structural Changes in Chromatin with Transcription in the Drosophila Heat-shock Response H. Biessmann, S. Wadsworth, B. Levy W., and B. J. McCarthy 829 An In Vitro Assay for the Specific Induction and Regression of Puffs in Iso- lated Polytene Nuclei of Drosophila melanogaster J. L. Compton and J. J. Bonnet 835 Distribution Patterns of Drosophila Nonhistone Chromosomal Proteins S. C. R. Elgin, L. A. Serunian, and L. M. Silver 839 The Expressed Portion of Eukaryotic Chromatin J. Bonner, R. B. Wallace, T D. Sargent, R. F. Murphy, and S. K. Dube 851 "Native" Salivary Chromosomes of Drosophila melanogaster R. J. Hill and F. Watt 859 CONTENTS xxi

The Size and Chromosomal Location of the 75S RNA Transcription Unit in Bal- biani Ring 2 B. Daneholt, S. T Case, J. Derksen, M. M. Lamb, L. Nelson, and L. Wieslander 867 Fate of Balbiani-ring RNA In Vivo J.-E. Edstr6m, E. Ericson, S. Lindgren, U. L6nn, and L. Rydlander 877 The Packaging Proteins of Core hnRNP Particles and the Maintenance of Prolif- erative Cell States W. M. LeStourgeon, A. L. Beyer, M. E. Christensen, B. W. Walker, S. M. Poupore, and L. P. Daniels 885 Substructure of Nuclear Ribonucleoprotein Complexes T Martin, P. Billings, J. Pullman, B. Stevens, and A. Kinniburgh 899 Free Informofers and Reconstitution of30S RNP V.V. Kulguskin, E. M. Lukani- din, and G. P. Georgiev 911

Cloned Eukaryotic Genes I The Cloning of Mouse Globin and Surrounding Gene Sequences in Bacterio- phage ~ P. Leder, S. M. Tilghman, D. C. Tiemeier, F. I. Polsky, J. G. Seidman, M. H. Edgell, L. W. Enquist, A. Leder, and B. Norman 915 Organization of Immunoglobulin Genes S. Tonegawa, C. Brack, N Hozumi, and V. Pirrotta 921 Studies on the Structure of Genes Expressed during Development G.K. Sire, A. Efstratiadis, C. W. Jones, F. C. Kafatos, M. Koehler, H. M. Kronenberg, T Maniatis, J. C. Regier, B. F. Roberts, and N. Rosenthal 933 Isolation and Characterization of the Silk Fibroin Gene with Its Flanking Se- quences Y. Suzuki and Y. Ohshima 947 Studies on the DNA Fragments of Mammals and Drosophila Containing Struc- tural Genes and Adjacent Sequences Y. V. Ilyin, N. A. Tchurikov, E. V. Ananiev, A. P. Ryskov, G. N. Yenikolopov, S. A. Limborska, N. E. Maleeva, V. A. Gvozdev, and G. P. Georgiev 959 Characterization and Kinetics of Synthesis of 15S ~-Globin RNA, a Putative Pre- cursor of ~-Globin mRNA P. J. Curtis, N. Mantei, and C. Weissmann 971 Globin mRNA Sequences: Analysis of Base Pairing and Evolutionary Impli- cations W. Salser 985 Physical Mapping of Repetitive DNA Sequences Neighboring the Rabbit ~-Globin Gene R. A. Flavell, A. J. Jeffreys, and G. C. Grosveld 1003

Cloned Eukaryotic Genes II Gene Organization in Drosophila A. Chovnick, M. McCarron, A. Hilliker, J. O'Donnell, W. Gelbart, and S. Clark 1011 The Two-dimensional Fractionation of Drosophila DNA S. S. Potter and C. A. Thomas, Jr. 1023 Sequence Homology within Families of Drosophila melanogaster Middle Repeti- tive DNA P.C. Wensink 1033 Isolation of a Telomeric DNA Sequence from Drosophila rnelanogaster G.M. Rubin 1041 The Organization of the Histone Genes in Drosophila melanogaster: Functional and Evolutionary Implications R. P. Lifton, M. L. Goldberg, R. W. Karp, and D. S. Hogness 1047 Repeated Gene Families in Drosophila melanogaster D. J. Finnegan, G. M. Ru- bin, M. W Young, and D. S. Hogness 1053 Short-period Repetitive-sequence Interspersion in Cloned Fragments of Sea Ur- chin DNA A. Shiu Lee, R. J. Britten, and E. H. Davidson 1065

Histone Genes Transcription of Xenopus tDNATet and Sea Urchin Histone DNA Injected into the Xenopus Oocyte Nucleus A. Kressmann, S. G. Clarkson, J. L. Telford, and M. L. Birnstiel 1077 xxii CONTENTS

The Histone H4 Gene of Strongylocentrotus purpuratus: DNA and mRNA Se- quences at the 5' End M. Grunstein and J. E. Grunstein 1083 Histone Gene Heterogeneity in the Sea Urchin Strongylocentrotus purpuratus E. S. Weinberg, G. C. Overton, M. B. Hendricks, K. M. Newrock, and L. H. Cohen 1093 The Localization of the Genes Coding for Histone H4 in Human Chromosomes L. C. Yu, P. Szabo, T W. Borun, and W. Prensky 1101 Regulation of Histone Gene Expression in HeLa Ss Cells G.S. Stein, J. L. Stein, W. D. Park, S. Detke, A. C. Lichtler, E. A. Shephard, R. L. Jansing, and I. R. Phillips 1107

Repeated DNA Sequences Fine Structure and Evolution of DNA in Heterochromatin W. J. Peacock, A. R. Lohe, W. L. Gerlach, P. Dunsmuir, E. S. Dennis, and R. Appels 1121 DNA Sequence Organization of Drosophila Heterochromatin D. Brutlag, M. Carlson, K. Fry, and T S. Hsieh 1137 Mammalian Repetitive DNA and the Subunit Structure of Chromatin P.R. Musich, F. L. Brown, and J. J. Maio 1147 Random Phasing of Polypyrimidine/PolypurineSegments and Nucleosome Mono- mers in Chromatin from Mouse L Cells H. C. Birnboim, R. M. Holford, and V. L. Seligy 1161 Ribosomal Genes and Their Proteins from Xenopus R. H. Reeder, H. L. Wahn, P. Botchan, R. Hipskind, and B. Sollner-Webb 1167 A Study of Early Events in Ribosomal Gene Amplification A.P. Bird 1179 Ribosomal DNA and Related Sequences in Drosophila rnelanogaster I.B. Dawid and P. K. Wellauer 1185 The Nucleotide Sequence of the Repeating Unit in the Oocyte 5S Ribosomal DNA of Xenopus laevis N. V. Fedoroff and D. D. Brown 1195 Simple Mendelian Inheritance of the Repeating Yeast Ribosomal DNA Genes T D. Petes, L. M. Hereford, and D. Botstein 1201

SEl~lmary The Molecular Biology of the Eukaryotic Genome Is Coming of Age P. Chambon 1209

Name Index 1235

Subject Index 1257 COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY

VOLUME XLII PART 2