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The Role of Histone H2av Variant Replacement and Histone H4 Acetylation in the Establishment of Drosophila Heterochromatin
The role of histone H2Av variant replacement and histone H4 acetylation in the establishment of Drosophila heterochromatin Jyothishmathi Swaminathan, Ellen M. Baxter, and Victor G. Corces1 Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218, USA Activation and repression of transcription in eukaryotes involve changes in the chromatin fiber that can be accomplished by covalent modification of the histone tails or the replacement of the canonical histones with other variants. Here we show that the histone H2A variant of Drosophila melanogaster, H2Av, localizes to the centromeric heterochromatin, and it is recruited to an ectopic heterochromatin site formed by a transgene array. His2Av behaves genetically as a PcG gene and mutations in His2Av suppress position effect variegation (PEV), suggesting that this histone variant is required for euchromatic silencing and heterochromatin formation. His2Av mutants show reduced acetylation of histone H4 at Lys 12, decreased methylation of histone H3 at Lys 9, and a reduction in HP1 recruitment to the centromeric region. H2Av accumulation or histone H4 Lys 12 acetylation is not affected by mutations in Su(var)3-9 or Su(var)2-5. The results suggest an ordered cascade of events leading to the establishment of heterochromatin and requiring the recruitment of the histone H2Av variant followed by H4 Lys 12 acetylation as necessary steps before H3 Lys 9 methylation and HP1 recruitment can take place. [Keywords: Chromatin; silencing; transcription; histone; nucleus] Received September 8, 2004; revised version accepted November 4, 2004. The basic unit of chromatin is the nucleosome, which is guchi et al. 2004). The role of histone variants, and spe- made up of 146 bp of DNA wrapped around a histone cially those of H3 and H2A, in various nuclear processes octamer composed of two molecules each of the histones has been long appreciated (Wolffe and Pruss 1996; Ah- H2A, H2B, H3, and H4. -
0612 US Synthetic Biology Symposium Final Agenda
Synthetic Biology for the Next Generation A Symposium Under the Auspices of The National Academy of Sciences and The National Academy of Engineering in conjunction with The Royal Society, The Royal Academy of Engineering, The Chinese Academy of Sciences, and The Chinese Academy of Engineering June 12-13, 2012 The National Academy of Sciences Building Auditorium 2101 Constitution Avenue, NW Washington, DC 20418 AGENDA Tuesday, June 12, 2012 7:30 Continental Breakfast 8:00 Welcome Charles Vest, President, The National Academy of Engineering 8:10 Meeting Global Challenges Moderator: Pamela Silver, Harvard Medical School Speakers: Daniel P. Schrag, Harvard University Saul Griffith, Engineer and Entrepreneur 9:00 Overview of Research in Key Application Areas Moderator: Guo-ping Zhao, Shanghai Institutes for Biological Sciences 1 Speakers: Jindong Zhao, Institute of Hydrobiology, Chinese Academy of Sciences (Agriculture and Environment) Gregory Stephanopoulos, Massachusetts Institute of Technology (Industrial Applications) Alexandra Daisy Ginsberg, Designer, Artist, and Writer (Arts/Humanities) Christina Smolke, Stanford University (Health and Medicine) 10:00 Discussion with Participants 10:15 Break 10:30 Organizational Strategies in Support of Synthetic Biology Moderator: Rob Carlson, Biodesic Speakers: Lionel Clarke, Shell Ian Fotheringham, Ingenza Jason Kelly, Ginkgo BioWorks Meagan Lizarazo, iGEM Darlene Solomon, Agilent Guo-ping Zhao, Shanghai Institutes for Biological Sciences 11:30 Discussion with Participants 11:45 Lunch 1:00 National -
TALE-Light Imaging Reveals Maternally Guided, H3k9me2/3-Independent Emergence of Functional Heterochromatin in Drosophila Embryos
Downloaded from genesdev.cshlp.org on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press TALE-light imaging reveals maternally guided, H3K9me2/3-independent emergence of functional heterochromatin in Drosophila embryos Kai Yuan and Patrick H. O’Farrell Department of Biochemistry, University of California at San Francisco, San Francisco, California 94158, USA Metazoans start embryogenesis with a relatively naïve genome. The transcriptionally inert, late-replicating het- erochromatic regions, including the constitutive heterochromatin on repetitive sequences near centromeres and telomeres, need to be re-established during development. To explore the events initiating heterochromatin forma- tion and examine their temporal control, sequence specificity, and immediate regulatory consequence, we estab- lished a live imaging approach that enabled visualization of steps in heterochromatin emergence on specific satellite sequences during the mid-blastula transition (MBT) in Drosophila. Unexpectedly, only a subset of satellite se- quences, including the 359-base-pair (bp) repeat sequence, recruited HP1a at the MBT. The recruitment of HP1a to the 359-bp repeat was dependent on HP1a’s chromoshadow domain but not its chromodomain and was guided by maternally provided signals. HP1a recruitment to the 359-bp repeat was required for its programmed shift to later replication, and ectopic recruitment of HP1a was sufficient to delay replication timing of a different repeat. Our results reveal that emergence of constitutive heterochromatin follows a stereotyped developmental program in which different repetitive sequences use distinct interactions and independent pathways to arrive at a heterochro- matic state. This differential emergence of heterochromatin on various repetitive sequences changes their replica- tion order and remodels the DNA replication schedule during embryonic development. -
Drosophila Ribosomal Proteins Are Associated with Linker Histone H1 and Suppress Gene Transcription
Downloaded from genesdev.cshlp.org on October 2, 2021 - Published by Cold Spring Harbor Laboratory Press Drosophila ribosomal proteins are associated with linker histone H1 and suppress gene transcription Jian-Quan Ni,1,3 Lu-Ping Liu,1,3 Daniel Hess,1 Jens Rietdorf,1 and Fang-Lin Sun1,2,4 1Friedrich Miescher Institute for Biomedical Research, Basel CH-4058, Switzerland; 2Institute of Epigenetics and Cancer Research, School of Medicine, Tsinghua University, Beijing 100080, China The dynamics and function of ribosomal proteins in the cell nucleus remain enigmatic. Here we provide evidence that specific components of Drosophila melanogaster ribosomes copurify with linker histone H1. Using various experimental approaches, we demonstrate that this association of nuclear ribosomal proteins with histone H1 is specific, and that colocalization occurs on condensed chromatin in vivo. Chromatin immunoprecipitation analysis confirmed that specific ribosomal proteins are associated with chromatin in a histone H1-dependent manner. Overexpression of either histone H1 or ribosomal protein L22 in Drosophila cells resulted in global suppression of the same set of genes, while depletion of H1 and L22 caused up-regulation of tested genes, suggesting that H1 and ribosomal proteins are essential for transcriptional gene repression. Overall, this study provides evidence for a previously undefined link between ribosomal proteins and chromatin, and suggests a role for this association in transcriptional regulation in higher eukaryotes. [Keywords: Ribosomal protein; L22; histone H1; chromatin; transcription] Supplemental material is available at http://www.genesdev.org. Received September 25, 2005; revised version accepted May 8, 2006. Transcription and translation in eukaryotes are generally discrete nuclear sites was sensitive to inhibitors of both believed to take place within two spatially separated cel- transcription and translation, arguing that the two pro- lular compartments. -
Introduction to the Genomics Education Partnership and Collaborative Genomics Research in Drosophila
Tested Studies for Laboratory Teaching Proceedings of the Association for Biology Laboratory Education Vol. 34, 135-165, 2013 Introduction to the Genomics Education Partnership and Collaborative Genomics Research in Drosophila Julia A. Emerson1, S. Catherine Silver Key2, Consuelo J. Alvarez3, Stephanie Mel4, Gerard P. McNeil5, Kenneth J. Saville6, Wilson Leung7, Christopher D. Shaffer7 and Sarah C. R. Elgin7 1Amherst College, Department of Biology, P.O. Box 5000, Amherst MA 01002 USA 2North Carolina Central University, Department of Biology, 2246 MTSB, Durham NC 27701 USA 3Longwood University, Department of Biological and Environmental Sciences, 201 High St., Farmville VA 23909 USA 4University of California San Diego, Division of Biological Sciences, 9500 Gilman Drive 0355, La Jolla CA 92093 USA 5York College/CUNY, Department of Biology, 94-20 Guy R. Brewer Blvd., Jamaica NY 11451 USA 6 Albion College, Biology Department, 611 E. Porter St., Albion MI 49224 USA 7Washington University, Department of Biology, Campus Box 1137, One Brookings Dr., St. Louis MO 3130 USA ([email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected]) The GEP, a group of faculty from over 90 primarily undergraduate institutions, is using comparative genomics to engage students in research within regular courses. Using a versatile curriculum, GEP undergraduates undertake projects to improve draft genomic sequences and/or participate in the annotation of these improved sequences. An additional goal of the annotation curriculum is for students to gain a sophisticated understanding of eukaryotic gene structure. Students do so by carefully mapping the protein-coding regions of putative genes from recently- sequenced Drosophila species. -
Workshop Notebook
GCAT WORKSHOPS 2009 NSF SUPPORTED DNA MICROARRAY WORKSHOPS FOR HISTORICALLY BLACK COLLEGES AND UNIVERSITIES, HISPANIC-SERVING INSTITUTIONS AND TRIBAL COLLEGES FACULTY JULY 5 - July 11, 2009 HOST INSTITUTION: MOREHOUSE COLLEGE BIOLOGY DEPARTMENT; ATLANTA, GA INSTRUCTORS Consuelo Alvarez, Malcolm Campbell, Todd Eckdahl, Edison Fowlks, Charles Hauser, Laurie Heyer, and Anne Rosenwald Genome Consortium for Active Teaching (GCAT) NSF GRANT DBI-0520908 Awarded to Hampton University PI: Edison R. Fowlks; Co-PIs: Mary Lee Ledbetter and Anne Rosenwald and NSF GRANT DBI-0520908 Awarded to Davidson College PI: Malcolm Campbell; Co-PIs: Laurie Heyer and Todd Eckdahl By the DIRECTORATE FOR BIOLOGICAL SCIENCES NATIONAL SCIENCE FOUNDATION DR. SALLY O’CONNOR, MANAGERING PROGRAM OFFICER NSF-SPONSORED GCAT DNA MICROARRAY SUMMER WORKSHOPS FOR UNDERGRADUATE HBCU, HSI AND TRIBAL COLLEGE FACULTY TAB I. Origin of this NSF Workshop and History of GCAT 1 II. Workshop Participants and Instructors 2 III. Workshop Schedule of Dry and Wet Lab Activities 3 IV. Assessment Material 4 A. Pre-Test B. Post-Test V. Wet Lab Activities 6 A. Culturing Yeast B. Isolating RNA C. 3DNA Protocol VI. Dry Lab Activities 7 A. Magic Tool User Guide B. Magic Tool: Exploring Diauxic Shift Microarray Data C. Exploring Correlations VII. Sampling of Microarray Articles 7 VIII. Notes, Special Instructions & Directions 8 ORIGIN OF THIS NSF WORKSHOP At a curriculum gathering during summer of 2004, Drs. Fowlks and Campbell presented their perspectives on the undergraduate educational implications of the NIH Roadmap. Fowlks addressed curricular changes in undergraduate biology, as well as recruitment and training for underrepresented populations. Campbell provided an overview of activities by GCAT, a non-profit educational consortium, to bring functional genomics methods into undergraduate courses and independent student research. -
Claire Barrett, Greg Creacy, Charles Hauser
Charles R. Hauser Associate Professor of Bioinformatics St. Edward’s University Voice: (512) 233.1671 Bioinformatics Program Fax. (512) 448.8764 Austin TX 78704 e-mail: [email protected] Professional Preparation University of Texas, Austin, TX 1972-1977 Botany University of Houston, TX 1984-1989 PhD. Biochemistry and Biophysics Duke University 1989-1995 Post-doctoral fellowship Appointments 2008 - Associate Professor Bioinformatics, St. Edward’s University 2004 - 2008 Assistant Professor Bioinformatics, St. Edward’s University 2000 - 2004 Research Scientist: Duke University, Durham NC 1995 - 2000 Research Associate: Duke University, Durham, NC 1989 - 1995 Postdoctoral Associate: Duke University, Durham, NC 1984 - 1989 Graduate Student/Researcher: University of Houston Awards and Honors 2016 St. Edward’s School of Natural Sciences Distinguished Research Award, 2015-16. 1990 NIH Postdoctoral Fellowship. Department of Botany, Duke University, Durham, NC. 1989 Hargitt Fellowship. Department of Zoology, Duke University, Durham, NC. Grants 2016 Howard Hughes Medical Institute (USE), Inclusive Excellence Grants 2017 Pre-proposal. Research L Kopec (PI), Charles R Hauser (collaborator) 2016 NSF, IUSE, “Integrating Bioinformatics into the Life Sciences—Phase 3” Mark Pauley (U. Nebraska, Omaha), Vince Buonaccorsi (Juniata College), Anya Goodman (California Polytechnic State University), Anne Rosenwald (Georgetown University) and Bill Tapprich (University of Nebraska at Omaha) Co-PIs. Charles Hauser (Advisory Committee Member). 2015 USDA, The Agricultural-STEM Pipeline: Progressive Experiential Learning Linking Three HSI Academic Tiers (Ag-STEM), 3 year ($275,000), Drs. O’Leary (PI), Quinn, Hauser, Deaton (co-PIs) 2015 NIH, “A Genome Browser On Ramp to Engage Biologists with Big Data”, Dr. Sarah Elgin, Washington University St. Louis (PI), Hauser (collaborator). -
Finding Genes in a New Fly Genome: Teaching About Genes/Genomes Via Bioinformatics Research
Finding Genes in a New Fly Genome: Teaching about Genes/Genomes via Bioinformatics Research Sarah Elgin, Anya Goodman, Wilson Leung Eric Tsoi, Charlene Emerson, David Carranza January 2012 Workshop Goals • Introduce Genomics Education Partnership • Hands-on practice with genome annotation • Discussion of curriculum options 3-week module ( ~10 hr: 1 lecture, 3X3 lab) 5-week – add a more difficult project 10-week - real research! • Scientific background on Drosophila genome • http://gep.wustl.edu [email protected] • Next workshops: June 24-26, August 19-22 (HHMI supported) Genomics Education Partnership (GEP) Goal: to engage students in a genomics research project, via a research-oriented AY lab course. Work organized through the GEP website. Our GEP research goal: Use comparative genomics to learn more about heterochromatic domains, analyzing the dot chromosomes and a control euchromatic region of Drosophila genomes Status Reference Completed Annotation Sequence Improvement New Project FlyBase: http://flybase.org I hear and I forget. I see and I remember. I do and I understand Confucius The scientific method allows ordinary people to do extraordinary things. Francis Bacon Genomics provides terrific opportunities to engage undergraduates in research! Strategy: divide and conquer! The D. mojavensis dot chromosome • Students completed 68 projects covering 1.7 Mb closing 26/28 gaps, adding ~15,000 bp and improving ~5000 bp. • Each project finished and annotated (all isoforms) twice; reconciliation for quality control done at Wash U Fosmid -
Heterochromatin-Associated Interactions of Drosophila Hp1a with Dadd1, HIPP1, and Repetitive Rnas
Downloaded from genesdev.cshlp.org on October 3, 2021 - Published by Cold Spring Harbor Laboratory Press Heterochromatin-associated interactions of Drosophila HP1a with dADD1, HIPP1, and repetitive RNAs Artyom A. Alekseyenko,1,2 Andrey A. Gorchakov,1,2,3 Barry M. Zee,1,2 Stephen M. Fuchs,4 Peter V. Kharchenko,5,6,7 and Mitzi I. Kuroda1,2,7 1Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA; 2Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA; 3Institute of Molecular and Cellular Biology, Novosibirsk 630090, Russia; 4Department of Biology, Tufts University, Medford, Massachusetts 02155, USA; 5Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA; 6Hematology/Oncology Program, Children’s Hospital, Boston, Massachusetts 02115, USA Heterochromatin protein 1 (HP1a) has conserved roles in gene silencing and heterochromatin and is also implicated in transcription, DNA replication, and repair. Here we identify chromatin-associated protein and RNA interactions of HP1a by BioTAP-XL mass spectrometry and sequencing from Drosophila S2 cells, embryos, larvae, and adults. Our results reveal an extensive list of known and novel HP1a-interacting proteins, of which we selected three for validation. A strong novel interactor, dADD1 (Drosophila ADD1) (CG8290), is highly enriched in heterochromatin, harbors an ADD domain similar to human ATRX, displays selective binding to H3K9me2 and H3K9me3, and is a classic genetic suppressor of position-effect variegation. Unexpectedly, a second hit, HIPP1 (HP1 and insulator partner protein-1) (CG3680), is strongly connected to CP190-related complexes localized at putative insulator sequences throughout the genome in addition to its colocalization with HP1a in heterochro- matin. -
2015 ANNUAL REPORT Executive Summary 2015 ANNUAL REPORT Executive Summary
2015 ANNUAL REPORT Executive Summary 2015 ANNUAL REPORT Executive Summary CONTENTS 2 PRESIDENT’S MESSAGE 7 RESEARCH Research Activities, 8 Research Investigators, 9 Research Highlights, 10 15 EDUCATION Educational Activities, 16 Education Highlights, 17 Meetings & Courses Program, 22 Cold Spring Harbor Laboratory Conferences, 22 Cold Spring Harbor Laboratory Courses, 24 Cold Spring Harbor Asia Conferences, 25 Banbury Center Meetings, 26 Front cover Photograph by Derek Hayn/Centerbrook Watson School of Biological Sciences, 27 This report is written and produced by CSHL Press Publications, 28 the Department of Public Affairs of Cold Spring Harbor Laboratory. For more information, 29 FINANCIAL REPORTS please contact: Chief Operating Officer’s Report, 30 Public Affairs Financial Statements, 32 Cold Spring Harbor Laboratory Consolidated Balance Sheet, 32 One Bungtown Road Cold Spring Harbor, NY 11724 Consolidated Statement of Activities, 33 Consolidated Statement of Cash Flows, 34 Cold Spring Harbor Laboratory (CSHL) is a 516.367.8455 private, not-for-profit research and education [email protected] www.cshl.edu 35 INSTITUTIONAL ADVANCEMENT institution at the forefront of efforts in molecular Institutional Highlights, 36 biology and genetics to generate knowledge Vice President, Communications Dagnia Zeidlickis Honor Roll of Donors, 37 that will yield better diagnostics and treatments Community Support, 42 for cancer, neurological diseases, and other Managing Editors Phil Renna Board of Trustees, 43 major causes of human suffering. Peter Tarr, Ph.D. Laboratory Leadership, 44 PRESIDENT’S MESSAGE to “spread the grants as widely as possible,” a form of scientific socialism that does not bode well for the fu- ture of American science. At the same time, however, opportunities abound in many areas of science, includ- ing cancer, neuroscience, plant biology and quantitative biology—areas of focus at Cold Spring Harbor. -
Harris H. Wang, Curriculum Vitae
Harris H. Wang, Curriculum Vitae Columbia University Office: 212-305-1697 Lasker, Rm 203BB Email: [email protected] Harris H. Wang 3960 Broadway Web: wanglab.c2b2.columbia.edu NY, NY 10032 CITIZENSHIP United States of America FIELD Systems and synthetic biology; Microbiome, Genome engineering; Microbial communities; Evolutionary biology; Functional genomics EDUCATION 2010 Harvard University Ph.D. in Biophysics 2010 Harvard-MIT Health Sciences and Technology Joint-Ph.D. in Medical Engineering Medical Physics (MEMP) 2005 Massachusetts Institute of Technology B.S. in Physics, B.S. in Applied Mathematics, minor in Biomedical Engineering PROFESSIONAL EXPERIENCE 3/2013 – Assistant Professor of Systems Biology present Department of Systems Biology Department of Pathology & Cell Biology Columbia University, College of Physicians and Surgeons, New York, USA 2010 – 2013 Wyss Technology Development Fellow (PI status) Instructor, Department of Systems Biology, Harvard Medical School Wyss Institute for Biologically Inspired Engineering, Harvard University. Faculty mentors: Jim J. Collins (BU), George M. Church, Don E. Ingber (HMS) Projects: Functional metagenomic reprogramming of the human microbiome; Engineered cooperativity in synthetic ecosystems. 2005 – 2010 NSF Graduate Research Fellowship NDSEG Graduate Research Fellowship Department of Genetics, Harvard Medical School, Boston, MA Ph.D. thesis advisor: George M Church Thesis committee: Jack Szostak (HMS), Jon Beckwith (HMS), David Liu (Harvard). Ron Weiss (MIT), Jim Hogle (HMS) Ph.D. thesis title: “Multiplex Automated Genome Engineering (MAGE) for the Optimization of Metabolic Pathways, Construction of New Genetic Codes, and Evolution of Synthetic Organisms.” 2008 Medical Clerkship, Mount Auburn Hospital, Cambridge, MA Advisor: Dr. Valerie Pronio-Stelluto Description: 3 month internal medicine rotation through HST MEMP Updated: 03/15/2018 Page 1 of 9 Harris H. -
Download the FREE HHMI Bulletin Ipad App from the Itunes App Store
HHMI BULLETIN A UG . ’11 VOL.24 • NO.03 • 4000 Jones Bridge Road Chevy Chase, Maryland 20815-6789 Hughes Medical Institute Howard www.hhmi.org Special Delivery What if a cancer patient’s own immune cells could be loaded with tumor-fighting drugs? Engineer and materials scientist Darrell Irvine has found a way. Irvine’s lab group has devised tiny drug-loaded nanoparticles and strapped hundreds of them to the surface of T-cell • lymphocytes. When tested in mice with metastatic melanoma, the www.hhmi.org enhanced T cells rapidly reproduced, moved through the body, and zeroed in on the spreading tumors. The tumors shrank and the mice lived longer than untreated mice. The team has also used the technique to send drug-studded blood stem cells to restore depleted bone marrow in mice. Fascinated by the complexity of the immune system, Irvine is working to remodel the surface of cells with synthetic materials to treat disease and reduce treatment side effects, with more applications in sight (see “T-Cell Booster Kits,” page 10). v ol. 24 / no. no. / Matthias Stephan / Irvine lab 03 ObservatiOns A GUIDInG LIGhT A motivated group of Harvard undergrads—all winners of elite high than that, however, if we are to account for the tens of thousands of school science fairs—decided to give back and share their advice and high school students who do research each year. experiences as competitors. Their book is half encouragement and half how-to. Early on, they reassure readers that scientists no longer fit By no means is research easy: it can be a substantial time commitment the stereotypical mold of “old, beaker-carrying men.” In fact, success- and quite frustrating at times.