Principal Investigator/Program Director:
BIOGRAPHICAL SKETCH
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NAME
Mary Ann Osley
POSITION TITLE
Professor
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing,
and include postdoctoral training.)
DEGREE
INSTITUTION AND LOCATION
(if applicable)
YEAR(s)
FIELD OF STUDY
Wheaton College, Norton, MA
B.A.
1967
Biology
Yale University, New Haven, CT
Ph.D.
1974
Microbiology
Princeton University, Princeton, NJ
Post-doc
1974-79
Molecular Biology
RESEARCH AND PROFESSIONAL EXPERIENCE:
A. Personal Statement
My research has long focused on the regulation of chromatin structure and function using budding yeast as a
model. My lab identified cis-acting regulatory elements that control transcription of the yeast histone genes
during the cell cycle, and defined the signals that activate transcription in late G1 and repress transcription in
response to a replication block. We isolated and characterized hir mutants, which are defective in histone
gene repression and whose wild type genes encode co-repressors that are subunits of an evolutionarily
conserved histone chaperone complex. I eventually switched my research focus to an analysis of the histone
proteins themselves. My lab identified mono-ubiquitylated H2B (H2Bub1) in yeast and showed that it is
regulated by the E2 ubiquitin conjugase, Rad6. Our research on H2Bub1 showed that it is regulated cotranscriptionally through the association of the ubiquitylation machinery with elongating RNA polymerase II.
We later showed that H2Bub1 contributes to chromatin stability by co-operating with the histone chaperone/reorganization factor, FACT, to reassemble nucleosomes displaced during transcription elongation. My lab’s
recent studies have identified a novel role for H2Bub1 in DNA replication following hydroxyurea-induced
replication stress. We have found H2Bub1 stabilizes the replisome by regulating pathways of histone
deposition onto newly synthesized DNA. We have additionally initiated a new project to define the epigenetic
landscape of stationary phase yeast cells, a model for the development of cellular quiescence.
B. Positions and Honors:
Professional Experiences:
1974 - 1979
Post-doctoral Fellow, Department of Biology, Princeton University
1974 - 1977
N.I.H. Postdoctoral Fellowship
1979 - 1987
Research Associate, Dana Farber Cancer Institute and Department of Microbiology and
Molecular Biology, Harvard Medical School
1987 - 1991
Assistant Member, Molecular Biology Program, Sloan Kettering Institute
1991 - 2000
Associate Member, Molecular Biology Program, Sloan Kettering Institute
1992 - 1995
Director of Molecular Biology Graduate Program, Sloan Kettering Institute-Cornell Univ.
School of Medicine
2000 - present
Professor, Molecular Genetics and Microbiology, University of New Mexico School of
Medicine
2004 – present Co-Director, Cancer Biology and Biotechnology Program, University of New Mexico Cancer
Center
Professional Activities:
1988 - 1990
Member, Editorial Board, Molecular and Cellular Biology
1989 - 1996
Organizer, NY Area Yeast Molecular Biology and Genetics meeting
1994 - 1997
Member, NIH Microbial Physiology and Genetics Study Section II
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Principal Investigator/Program Director:
2000 - 2004
2005, 2006
2004 – present
2006 – present
2009 - present
2007- 2011
1988 – Present
Member, NCI Special Manpower Training Study Section, Subcommittee F
Ad-hoc Member, NCI Special Manpower Training Study Section, Subcommittee F
Ad-hoc Member, NSF Biochemistry of Gene Expression review panel
Member, Editorial Board, Molecular and Cellular Biology
Member, Editorial Board, BBA Gene Regulatory Mechanisms
Member, NIH MGC Study Section
Reviewer: Cell, Mol. Cell, Science, Nature, Nature Struct. & Mol. Biol., Nature Cell Biol.,
Genes Dev., Curr. Biol., Mol. Cell. Biol., Genetics, Proc. Natl. Acad. Sci. USA, EMBO J.,
Nuc. Acids Res., Eukaryotic Cell, BBA Gene Reg Mech, PLoS Journals, J Cell Biol
C. Relevant Peer-Reviewed Publications:
1. Dimova D, Nackerdien Z, Furgeson S, Eguchi S and Osley MA: Role for transcriptional repressors in
targeting the yeast Swi/Snf complex. Mol. Cell, 4: 75-83, 1999.
2. Robzyk K, Recht J and Osley MA: Rad6-dependent ubiquitination of histone H2B in yeast. Science, 287:
501-504, 2000.
3. Sutton A, Bucaria J, Osley MA and Sternglanz R: Yeast ASF1 protein is required for cell cycle regulation
of histone gene transcription. Genetics, 158: 587-596, 2001.
4. Martini EM, Keeney S and Osley MA: A role for histone H2B during repair of UV-induced DNA damage in
Saccharomyces cerevisiae. Genetics, 160: 1375-1387, 2002.
5. Sharp JA, Franco A, Osley MA and Kaufman PD: Chromatin Assembly Factor-I and Hir proteins contribute
to building kinetochores in Saccharomyces cerevisiae. Genes Dev., 16: 85-100, 2002.
6. Henry, K., Wyce, A., Lo, W.-S., Duggan, L., Emre, T., Kao, C.F., Pillus, L., Shilatifard, A., Osley, MA, and
Berger, SL: Transcriptional activation via sequential histone H2B ubiquitylation and deubiquitylation,
mediated by SAGA-associated Ubp8. Genes Dev 17: 2648-2663, 2003.
7. Kao, C.F., Hillyer, C., Tsukuda, T., Henry, K., Berger, S., and Osley, MA: Rad6 plays a role in
transcriptional activation through ubiquitylation of H2B. Genes Dev. 18: 184-195, 2004
8. Xiao, X, Kao, CK, Krogan, N, Greenblatt, J, Sun, ZW, Osley, MA, and Strahl, B: Rad6-dependent
ubiquitylation of H2B is associated with elongating RNA polymerase II. Mol. Cell. Biol. 25: 637-651, 2005.
9. Tsukuda, T, Fleming, A, Nickoloff, J.A, and Osley, MA: Chromatin remodeling at a DNA double-strand
break site in Saccharomyces cerevisiae. Nature 438: 379-383, 2005.
10. Fleming, AB, Kao, C-F, Hillyer, C, Pikaart, M, and Osley, MA: H2B ubiquitylation plays a role in
nucleosome dynamics during transcription elongation. Mol Cell 31: 57-66, 2008.
11. Tsukuda, T, Lo, Y-C, Krishna, S, Sterk, R, Osley, MA, and Nickoloff, J: INO80-dependent chromatin
remodeling regulates early and late stages of mitotic homologous recombination. DNA Repair 8: 360-360,
2009.
12. Nakanishi, S, Lee, JS, Gardner, JM, Takahashi, Y, Chandrasekharan, Sun, ZW, Osley, MA, Strahl, B,
Jasperson, SL, Shilatifard, A: Histone H2BK123 monoubiquitination is the critical determinant for H3K4 and
H3K79 trimethylation by COMPASS and Dot1. J Cell Biol 186: 371-377, 2009.
13. Amin, A, Dimova, D, Ferreira, M, Vishnoi, M, Hancock, L, Osley, MA*, and Prochasson, P*. The mitotic
Clb cyclins are required to alleviate HIR-mediated repression of the yeast histone genes at the G1/S
transition. BBAGRM. 1819: 16-27, 2012.
14. Shieh, GS, Pan, C-H, Wu J-H, Sun, Y-J, Chang, K-W, Tung, L, Chang, T-H, Fleming, A, Hillyer, C, Berger,
SL, Osley, MA* and Kao, C-K*: H2B ubiquitylation is part of chromatin architecture that marks exon-intron
structure in budding yeast. BMC Genomics 12: 627, 2011.
15. Trujillo, KM and Osley, MA: A role for H2B ubiquitylation in DNA replication, Mol Cell, 48: 734-746, 2012.
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Principal Investigator/Program Director:
D. Research Support:
Active:
NIH GM40118-22
Title: “ “Genetic Analysis of H2B Ubiquitylation”.
PI: Mary Ann Osley
Period: 08-01-12 through 07/31/16
Direct costs: $239,000 per year
This grant supports research to examine the role of H2B ubiquitylation in transcription, replication, and
chromatin stability, and to define the epigenetic landscape of quiescent yeast cells.
Pending:
NIH AG044354-01
Title: “Contributions of epigenetics to cellular quiescence and chronological aging”
PI: Mary Ann Osley
Period: 12/01/12 through 11/31/17
Direct costs: $250,000 per year
This grant will support studies to define the role of histone modifications in the development and survival of
quiescent cells formed during chronological aging.
Completed:
NIH CA118357-05
Title: “Chromatin Regulation of Double-Strand Break Repair”
PI: Mary Ann Osley
Period: 02/01/06 through 01/31/11
Direct costs: $172,500 per year
This grant supported research on the role of chromatin remodeling in the repair of DNA double-strand breaks.
NSF MCB-9986650
Title: “Roles of Histone Ubiquitination in Yeast”
PI: Mary Ann Osley
Period: Feb. 1, 2000-March 31, 2001
Total costs: $100,346
This grant supported a pilot study to characterize the factors regulating H2B ubiquitylation in yeast. This
research was subsequently folded into NIH GM40118.
HFSPRG254/97
Title: “HIR Proteins in Chromatin Assembly, Transcriptional Regulation, and Development”
PI: Marc Lipinski (France)
Period: Oct. 1, 1997-February 28, 2001
Total costs: $720,000; $126,000 total Osley share
This was a collaborative, international grant from the Human Frontiers of Science Program to support research
on the evolutionarily conserved HIR proteins that my laboratory originally identified in yeast.
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