COLD SPRING HARBOR LABORATORY CSH 1995 SPRING COURSES

ADVANCED GENOME CLONING & ANALYSIS OF SEQUENCING & ANALYSIS LARGE DNA MOLECULES March 14 - 27 March 30 - April 12

Ellson Y. Chen, Perkin Elmer Corporation Hadi Abderrahim, Cell Genesys, Inc. Richard Gibbs, Baylor College of Medicine Bruce Birren, Whitehead / MIT Center for Genome Research W. Richard IMcCombie, Cold Spring Harbor Laboratory Douglas Vollrath, Stanford University Richard K. Wilson, Washington University This course will cover the theory and practice of manipulating and dor Recent advances in the automation of DNA sequencing have opened new high molecular weight DNA. The course will focus on the use of yeast possibilities for the analysis of complex genomes at the DNA sequence level. artificial chromosome (YAC), bacterial artificial chromosome (BAG) an This two week course will provide intensive training in this rapidly evolving bacteriophage P1 cloning systems for library construction and techniqi field. The course will emphasize techniques and strategies for using of pulsed field gel electrophoresis (PFGE). Lectures and laboratory w( automated sequencers to sequence large, contiguous genomic regions. will include an introduction to yeast genetics, the isolation and manipul Students will carry out all of the steps in the sequencing process from of high molecular weight DNA from a variety of sources, and preparati^ preparing cosmid DNA to computer analysis of the finished sequence. and analytical PFGE. Clones will be produced and characterized by Topics will include subclone library generation, large-scale template several approaches, including library screening, contig assembly, long purification, sequencing reactions, gel analysis on automated sequencers, range restriction mapping, and recovery of YAC ends. Lectures by ou sequence assembly, gap filling and conflict resolution. Students will work speakers on topics of current interest will supplement the laboratory w in groups to sequence a large region of DNA and through this process be trained in crucial project and data management techniques. A series of lecturers will discuss their applications of these techniques as well as alternate strategies for high speed automated DNA sequencing. EARLY DEVELOPMENT OF XENOPUS LAEVIS PROTEIN PURIFICATION & April 4 -13 Robert Grainger, University of Virginia CHARACTERIZATION Hazel Sive, Whitehead Institute March 30 - April 12 This course will provide extensive laboratory exposure to the biology, Richard Burgess, University of Wisconsin, Madison manipulation and use of embryos from the frog, Xenopus laevis. The James Kadonaga, University of California, San Diego course is suited both for investigators who have had no experience wil Sue-Hwa Lin, M.D. Anderson Cancer Center, University of Texas Xenopus, as well as those who have worked with Xenopus and wish tc Daniel R. Marshak, Cold Spring Harbor Laboratory expand their repertoire of techniques. All students should have a cum training in molecular biology and some knowledge of developmental bi This course is intended for scientists who are not familiar with techniques of The course consists of intensive laboratory sessions, supplemented b; protein isolation and characterization. It is a rigorous program that includes daily lectures and demonstrations from experts in both experimental ai laboratory work all day and a lecture with discussion session every evening. molecular embryology. Six areas will be covered: (i) care and handlinj Each student will become familiar with each of the major techniques in protein adults and embryo isolation; (ii) stages of embryonic development and purification by actually performing four separate isolations including: (i) a anatomy; (iii) whole mount in situ hybridization and immunocytochemis regulatory protein from muscle tissue; (ii) a sequence-specific, DNA-binding (iv) microinjection of eggs and oocytes, including mRNA and antisens« protein; (iii) a recombinant protein overexpressed in E. coli; and (iv) a oligonucleotides; (v) micromanipulation of embryos, including inductior membrane-bound receptor. A variety of bulk fractionation, electrophoretic, and and transplantation assays; and (vi) preparation and use of cell cycle chromatographic techniques will be employed including: precipitation by salts, extracts. Lecturers and co-instructors will include: Enrique Amaya, Ric pH, and ionic polymers; ion exchange, gel filtration, hydrophobic interaction, Elinson, Janet Heasman, John Gurdon, Richard Harland, Ray Keller, and reverse phase chromatography; lectin affinity, oligonucleotide affinity, and John Newport, and Nancy Papalopulu. immunoaffinity chromatography; polyacrylamide gel electrophoresis, and electroblotting; and high performance liquid chromatography. Procedures will be presented for solubilizing proteins from inclusion bodies and refolding them Application Deadline: January 15,1995 into active monomeric forms. Methods of protein characterization will be Tuition Room and Board: utilized including immunological and biochemical assays, peptide mapping, amino acid analysis, protein sequencing, and mass spectrometry. Emphasis Ten day course $ 1,460 will be placed on strategies of protein purification and characterization rather Two week course $ 1,720 than on automated instrumental analysis. Guest lecturers will discuss protein structure, modifications of proteins, methodologies for protein purification and Scholarship funds are available for qualified applicants characterization, and applications of protein biochemistry to cell and molecular biology. Guest lecturers have included: R. Aebersold, L. Gierasch, G. Hart, A. Kornberg, N. Pace, Y. Paterson, G. Rose, J. Rothman, B. Stillman, and N. Tonks. Applications can be obtained from: Course Registrar GM Cold Spring Harbor Laboratory' 1 Bungtown Road, Cold Spring Harbor, New York 11724-2213 Tel: 516-367-8345 Fax: 516-367-8845 Email: meetingsr«}cshl.org Additional information on Meetings, Courses, and Publications: World Wide Web site http://www.cshl.o Reader Service No. 260 GENES

DEVELOPMENT

VOLUME 8 NUMBER 22 PAGES 2665-2792 NOVEMBER 15, 1994

EDITORIAL BOARD J. Adams (Melbourne, Australia) N. Jones (London, UK) Editors J. Beckwith (Boston, USA) J. Kadonaga (La Jolla, USA) T. Grodzicker (Cold Spring Harbor) T. Cech (Boulder, USA) R. Lehmann (Cambridge, USA) N. Hastie (Edinburgh) P. Chambon (Strasbourg, France) M. Levine (San Diego, USA) N.-H. Chua (New York, USA) D. Livingston (Boston, USA) Managing Editor E. Coen (Norwich, UK) R. Losick (Cambridge, USA) J. Cuddihy (Cold Spring Harbor) J. Coffin (Boston, USA) J. Manley (New York, USA) S. Courtneidge (Heidelberg, FRG) W. McGinnis (New Haven, USA) E. De Robertis (Los Angeles, USA) S. McKnight (South San Francisco, USA) R. Evans (La JoUa, USA) A. McMahon (Cambridge, USA) G. Fink (Cambridge, USA) P. Nurse (London, UK) P. Goodfellow (Cambridge, UK) C. Niisslein-Volhard (Tubingen, FRG) S. Gottesman (Bethesda, USA) R. Palmiter (Seattle, USA) T. Graf (Heidelberg, FRG) L. Parada (Dallas, USA) C. Gross (San Francisco, USA) C. Prives (New York, USA) R. Grosschedl (San Francisco, USA) G. Rubin (Berkeley, USA) F. Grosveld (Rotterdam, The Netherlands) U. Schibler (Geneva, Switzerland) M. Groudine (Seattle, USA) D. Solter (Freiburg, FRG) L. Guarente (Cambridge, USA) P. Soriano (Seattle, USA) R. Harland (Berkeley, USA) J. Steitz (New Haven, USA) E. Harlow (Charlestown, USA) T. Taniguchi (Osaka, Japan) W. Herr (Cold Spring Harbor, USA) S. Tilghman (Princeton, USA) J. Hodgkin (Cambridge, UK) R. Tjian (Berkeley, USA) R. Horvitz (Cambridge, USA) E. Wagner (Vienna, Austria) P. Ingham (London, UK) V. Walbot (Stanford, USA) T. Jessell (New York, USA) M. Wigler (Cold Spring Harbor, USAl

EDITORIAL OFFICES Editorial/Production United States United Kingdom N. Dumser, Technical Editor Cold Spring Harbor Laboratory Press MRC Human Genetics Unit V. Nicolette, Production Editor Box 100, 1 Bungtown Road Western General Hospital L. Olsewski, Editorial Secretary Cold Spring Harbor, New York 11724-2203 Crewe Road Phone 516-367-8492 Edinburgh EH4 2XU, UK FAX 516-367-8532 Phone 031-332-8676 FAX 031-332-7359

GENES & DEVELOPMENT (ISSN 0890-9369) Is published semimonthly for $450 Veronica van Heyningen, MRC Human Genetics Unit, Western General (institutional), $115 (individual making personal payment), $159 (Genet- Hospital, Crewe Road, Edinburgh EH4 2XU, UK. ical Society of Great Britain members) by Cold Spring Harbor Laboratory Claims for missing issues must be received within 4 months of issue Press, Bungtown Road, Cold Spring Harbor, New York 11724, in associ­ date. ation with the Genetical Society of Great Britain. Second-class postage is paid at Cold Spring Harbor and additional mailing offices. POSTMAS­ Change of address Please enclose recent mailing label with address TER: Send address changes to Cold Spring Harbor Laboratory Press, POB change; allow 4 weeks. 100, 1 Bungtown Rd., Cold Spring Harbor, New York 11724-2203. Advertising To advertise in Genes Sk Development, contact Nancy Subscription Price Orders may be sent to Cold Spring Harbor Labora­ Kuhle, Advertising Manager, Cold Spring Harbor Laboratory Press, Cold tory Press, Fulfillment Department, 10 Skyline Drive, Plain view, NY Spring Harbor, New York 11724-2203; telephone 516-367-8351. 11803-9729. Telephone: Continental US except NY State, 1-800-843- Photo Copy Authorization to photocopy items for internal or personal 4388; all other locations, 516-349-1930/1931/1932. FAX 516-349-1946. use, or the internal or personal use of specific clients, is granted by Cold Volume 8, 1994, $450, U.S. institutional; $540, R.O.W. institutional. Spring Harbor Laboratory Press for libraries and other users registered Personal subscription rate: $115, U.S.; $205, R.O.W. Price includes sur­ with the Copyright Clearance Center (CCC) Transactional Reporting face postage for U.S. and airlift for R.O.W. Genetical Society members, Service, provided that the base fee of $5.00 per copy is paid directly to $159.00. All subscriptions are entered for the calendar year and must be CCC, 21 Congress St., Salem, MA 01970 (0890-9369/94 $5.00 -I- 0.). This prepaid. Personal subscriptions must be prepaid by personal check, consent does not extend to other kinds of copying, such as copying for credit card, or money order. All checks must be for US dollars and drawn general distribution for advertising or promotional purposes, for creating on a US bank. Genetical Society members may also subscribe by check, new collective works, or for resale. payable to the Genetical Society, for £115 (includes airlift). Send to: Dr. Copyright © 1994 by Cold Spring Harbor Laboratory Press GEIVES & DEVELOPMENT November 15,1994 Contents

Research papers E2F-4, a new member of the E2F transcription factor family, interacts with pi07 2665 Doron Ginsberg, Gino Vairo, Thomas Chittenden, Zhi-Xiong Xiao, Gangfeng Xu, Karen L. Wydner, James A. DeCaprio, Jeanne B. Lawrence, and David M. Livingston

E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with pl07 2680 in vivo Roderick L. Beijersbergen, Ron M. Kerkhoven, Liang Zhu, Leone Carlee, P. Mathijs Voorhoeve, and Rene Bernards

Development of several organs that require inductive epithelial-mesenchymal interactions is 2691 impaired in I£F-i-deficient mice Courtney van Genderen, Ross M. Okamura, Isabel Farinas, Rong-Guo Quo, Tristram G. Parslow, Laurakay Bruhn, and Rudolf Grosschedl

SR proteins can compensate for the loss of Ul snRNP functions in vitro 2704 Woan-Yuh Tarn and Joan A. Steitz

Direct control of transcription of the Drosophila morphogen bicoid by the Serendipity 8 zinc 2718 finger protein, as revealed by in vivo analysis of a finger swap Fran9ois Payre, Michele Crozatier, and Alain Vincent

Negative regulation of proneural gene activity: hairy is a direct transcriptional repressor 2729 of achaete Mark Van Doren, Adina M. Bailey, Joan Esnayra, Kekoa Ede, and James W. Posakony

Hairy function as a DNA-binding helix-loop-helix repressor of Drosophila sensory 2743 organ formation Shunji Ohsako, Jeanette Hyer, Grace Panganiban, Ian Oliver, and Michael Caudy

Multiple regions of TBP participate in the response to transcriptional activators in vivo 2756 William P. Tansey, Siegfried Ruppert, Robert Tjian, and Winship Herr micropbtbalmia, a critical factor in melanocyte development, defines a discrete transcription 2770 factor family Timothy J. Hemesath, Eirikur Steingrimsson, Gael McGill, Michael J. Hansen, James Vaught, Colin A. Hodgkinson, Heinz Arnheiter, Neal G. Copeland, Nancy A. Jenkins, and David E. Fisher

Novel mechanism of C/EBPp (NF-M) transcriptional control: activation through derepression 2781 Elisabeth Kowenz-Leutz, Geraldine Twamley, Stephane Ansieau, and Achim Leutz

Corrigendum 2792

Cover Role of LEF-1 in organogenesis in mice. [Inset] Wild-type hair follicle [left]-, arrest in hair follicle development in LEF-1-deficient mice [light). [Background] Neurons of trigeminal system. (For details, see van Genderen et al., p. 2691.)