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Michael Grunstein, Ph.D.

Work Email Address:
mg@mbi.ucla.edu Laboratory Address:
Laboratory
Boyer Hall
Los Angeles, CA 90095
UNITED STATES

Work Address:
Boyer Hall Rm 302
611 Young Drive East
UCLA
Los Angeles, CA 90095
UNITED STATES

Office
Boyer Hall
Los Angeles, CA 90095
UNITED STATES


Work Phone Number:
(310) 825-0840

Web Address:
The Grunstein Lab
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Michael Grunstein, Ph.D.

Department / Division Affiliations
Distinguished Professor, Biological Chemistry
Member, Genetics & Genomics GPB Home Area, JCCC Gene Regulation Program Area
Faculty, Molecular Biology IDP

Awards

2012 Thomson-Reuters Citation Laureate (with David Allis)
2011 Rosenstiel Award for Distinguished Work in Basic Medical Research (with David Allis)
2008 Benzon Symposium Speaker, Copenhagen, Denmark
2008 Elected to the National Academy of Sciences
2007 The 17th Beckman Symposium. The Changing Face of Chromatin
1998-2007 MERIT Award, National Institutes of Health
2006 Friedrich Miescher Institute, Basel, Science Colloquium Speaker
2005 Novum Lecture, Karolinska Institute, Stockholm
2004 Marian Koshland Lecturer, UC Berkeley
2001-2004 International Scientific Advisory Board Member. Wellcome Trust Center for Cell Biology, University of Edinburgh, Scotland
2003 Awarded Massry Prize (with Roger Kornberg and David Allis)
2001 Elected Fellow of the American Academy of Arts and Science
2000 Keynote Speaker, Euresco Conference, Gene Transcription in Yeast: Transcriptional Regulation and Chromatin Structure, Castelvecchio Pascoli, Italy
2000 Royal Swedish Society of Sciences Lecture
1999 Keynote Speaker, Chromatin Structure and Regulation, Keystone Symposium, Santa Fe, New Mexico
1998 Markey Distinguished Speaker, University of Southern California
1995 Keynote Speaker, Keystone Symposium, Epigenetic Regulation of Transcription, Hilton Head Island, South Carolina
1994 Chair, Gordon Conference, Nuclear Proteins
1985 Chair, Chromosome Structure and Expression Conference, Cold Spring Harbor
1979-1984 American Cancer Society Faculty Research Award
1976-1979 Awardee March of Dimes Basil O'Connor Starter Research Grant
1972-1974 Leukemia Society of America Fellow
1969-1971 Wellcome Trust Studentship Award

Research Interest:

Michael Grunstein studies how histones and their post-translational modifications regulate chromosomal functions. It had been known since the 1960s that histone acetylation and gene activity were correlated but it was not known whether changes in chromatin structure and in particular histone acetylation are a cause or result of transcription. The Grunstein lab pioneered the use of genetics in analyzing histone protein function in yeast in the early 1980s. This analysis was to show that nucleosomes are repressors of transcription initiation in living cells and that acetylation sites at the histone N termini are required for gene activity. Moreover his lab demonstrated in 1995 that non-histone regulatory proteins bind histones to regulate heterochromatin formation. This allowed the lab to determine how an acetylation site (histone H4 K16) at the H4 N terminus regulates the initiation, spreading and the barrier to spreading of heterochromatin.

At present the Grunstein laboratory uses genetics, genome wide and gene specific biochemical approaches to study how histones regulate the binding of regulatory enzymes and structural factors to chromatin. His lab's findings include the role of histone deacetylation in regulating the timing of DNA replication, the role of deacetylation in gene activity and the genome wide division of labor for histone deacetylases and histone acetylation sites in yeast. Recent studies from the Grunstein lab have uncovered the acetylation of a novel site histone H3 K56 in yeast and its role in transcription and heterochromatin silencing. The modification of this site that also regulates yeast histone assembly, DNA replication and DNA repair is currently a focus of the lab in studying the differentiation of human stem cells.



Biography:

Michael Grunstein is Distinguished Professor of Biological Chemistry at the Geffen School of Medicine at UCLA. He was born in Romania, obtained his BSc degree from McGill University in Montreal, the PhD degree from the University of Edinburgh, Scotland and did his post-doctoral training at Stanford University in Palo Alto, California where he invented the Colony Hybridization screening technique of recombinant DNAs in David Hogness'a laboratory. Soon after coming to UCLA in 1975 he pioneered the genetic analysis of histones in yeast and showed for the first time that histones are regulators of gene activity in living cells. He now studies the means by which histone modifications regulate gene activity in yeast and human cells.

Publications:

Tan Yuliang, Xue Yong, Song Chunying, Grunstein Michael Acetylated histone H3K56 interacts with Oct4 to promote mouse embryonic stem cell pluripotency. Proceedings of the National Academy of Sciences of the United States of America. 2013; 110(28): 11493-8.
Grunstein Michael, Gasser Susan M Epigenetics in Saccharomyces cerevisiae. Cold Spring Harbor perspectives in biology. 2013; 5(7): .
Yu Yongxin, Song Chunying, Zhang Qiongyi, DiMaggio Peter A, Garcia Benjamin A, York Autumn, Carey Michael F, Grunstein Michael Histone H3 lysine 56 methylation regulates DNA replication through its interaction with PCNA. Molecular Cell. 2012; 46(1): 7-17.
Kitada Tasuku, Kuryan Benjamin G, Tran Nancy Nga Huynh, Song Chunying, Xue Yong, Carey Michael, Grunstein Michael Mechanism for epigenetic variegation of gene expression at yeast telomeric heterochromatin. Genes & development. 2012; 26(21): 2443-55.
Chen Xiao-Fen, Kuryan Benjamin, Kitada Tasuku, Tran Nancy, Li Jing-Yu, Kurdistani Siavash, Grunstein Michael, Li Bing, Carey Michael The Rpd3 core complex is a chromatin stabilization module. Current biology : CB. 2012; 22(1): 56-63.
Adam S. Sperling, Kyeong Soo Jeong, Tasuku Kitada and Michael Grunstein Topoisomerase II binds nucleosome-free DNA and acts redundantly with Topoisomerase I to enhance recruitment of RNA Pol II in budding yeast . Proc. Nat. Acad. Sci. USA 2011; 108: 12693-8.
Kitada, T., Schleker, T., Sperling. A.S., Xie, W., Gasser, S.M. and Grunstein, M. gH2A is a component of yeast heterochromatin required for telomere elongation. Cell Cycle 2011; 10(2): 1-8.
Indranil Sinha, Luke Buchanan, Carolina Bonilla, Michelle Rönnerblad, Andrej Shevchenko, Michael Grunstein, A. Francis Stewart and Karl Ekwall Genome wide mapping of histone modifications and mass spectrometry reveal a function for the histone H4 acetylation zip and a role for H3K36 methylation at gene promoters in fission yeast. Epigenomics 2010; 2: 377-393.
Sun W, Xie W, Xu F, Grunstein M, Li KC. Dissecting nucleosome free regions by a segmental semi-Markov model. . PLoS ONE 2009; 4(3): e4721. Epub 2009 Mar 6..
Xie, W., Song, C., Sperling, A., Xu, F., Sridharan, R., Conway, A., Plath, K., Clark, A., and Grunstein, M. Histone H3 K56 acetylation is linked to the core transcriptional network for pluripotency in human embryonic stem cells. Molecular Cell 2009; 33: 417-427.
Sperling, A. and Grunstein, M. Histone H3 N-terminus regulates higher order structure of yeast heterochromatin. . PNAS 2009; 106: 13153-13159 .
Chin MH, Mason MJ, Xie W, Volinia S, Singer M, Peterson C, Ambartsumyan G, Aimiuwu O, Richter L, Zhang J, Khvorostov I, Ott V, Grunstein M, Lavon N, Benvenisty N, Croce CM, Clark AT, Baxter T, Pyle AD, Teitell MA, Pelegrini M, Plath K, Lowry WE. Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell 2009; 5: 111-23.
Jonathan Houseley, Liudmilla Rubbi, Michael Grunstein, David Tollervey, and Maria Vogelauer A ncRNA Modulates Histone Modification and mRNA Induction in the Yeast GAL Gene Cluster. Molecular Cell 2008; 32: 685-695.
Gregory A. Horwitz, Kangling Zhang, Matthew A. McBrian, Michael Grunstein, Siavash K. Kurdistani, & Arnold J. Berk Adenovirus small e1a alters global patterns of histone modification. . Science 2008; 321: 1084-1085.
Tommy Kaplan, Chih Long Liu, Judith A. Erkmann, John Holik, Michael Grunstein, Paul D. Kaufman, Nir Friedman, Oliver J. Rando Cell Cycle? and Chaperone-Mediated Regulation of H3K56ac Incorporation in Yeast. . PLoS Genetics 2008; 4(11 ): 1-16. Publ.on-line..
Sahbazian, M. D. and Grunstein, M. Functions of site-specific histone acetylation and deacetylation. . Annual Reviews of Biochemistry 2007; 76: 26.1-26.26.
Xu, F., Zhang, Q., Zhang, K., Xie, W. and Grunstein, M. Sir2 deacetylates histone H3 lysine 56 to regulate telomeric heterochromatin structure in yeast . Molecular Cell 2007; 27: 890-900.
Mickael Durand-Dubief, Indranil Sinha, Fredrik Fagerstrom-Billai, Carolina Bonilla, Anthony Wright, Michael Grunstein, Karl Ekwall Specific functions for the fission yeast Sirtuins Hst2 and Hst4 in gene regulation and retrotransposon silencing . EMBO J. 2007; 26: 2477-2488.
Millar CB, Xu F, Zhang K, Grunstein M Acetylation of H2AZ lysine 14 is associated with genome-wide gene activity in yeast. Genes and Development 2006; 20: 711-722.
Grunstein M, Gasser S Epigenetics in Saccharomyces cerevisiae: Chapter 4. Epigenetics 2006; 63-79.
Millar CB, Grunstein M Genome wide patterns of histone modifications in yeast. Nature Reviews Molecular Cell Biology 2006; 7: 657-666.
Ahn, S., Diaz, R. L. Grunstein, M. and Allis, C. D. Histone H2B deacetylation at lysine 11 is required for yeast apoptosis induced by phosphorylation of H2B at serine 10. . Molecular Cell 2006; 24: 211-220.
Xu F, Zhang K, Grunstein M Acetylation in histone H3 globular domain regulates gene expression in yeast. Cell. . 2005; 121(3): 375-85.
Xu, F., Zhang, K. and Grunstein, M. Acetylation in the histone H3 globular domain regulates gene expression in yeast. Cell 2005; 121: 375-385.
Keogh MS, Kurdistani SK, Morris SA, Ahn SH, Collins SR, Podolny V, Chin K, Punna T, Thompson NJ, Boone C, Emili A, Weissman JS, Hughes TR, Strahl BD, Grunstein M, Greenblatt JF, Buratowski S, Krogan NJ Co-transcriptional Set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex. Cell 2005; 123: 593-605.
Wiren M, Silverstein R, Sinha I, Walfridsson J, Lee H, Laurenson P, Pillus L, Robyr D, Grunstein M, Ekwall K Genome wide analysis of nucleosome density, histone acetylation and HDAC function in fission yeast . EMBO J. 2005; 24: 2906-2918.
Seligson DB, Horvath S, Shi T, Yu H, Tze S, Grunstein M, Kurdistani SK Global histone modification patterns predict risk of prostate cancer recurrence. Nature. . 2005; 435(7046): 1262-6.
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Shahbazian MD, Zhang K, Grunstein M Histone H2B ubiquitylation is dispensable for mono-methylation but important for subsequent rounds of methylation by Dot1 and Set1. Molecular Cell 2005; 19: 271-277.
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Robyr D, Kurdistani SK, Grunstein M Analysis of genome-wide histone acetylation state and enzyme binding using DNA microarrays. Methods in enzymology. . 2004; 376: 289-304.
Kurdistani SK, Tavazoie S, Grunstein M Mapping global histone acetylation patterns to gene expression. Cell. . 2004; 117(6): 721-33.
Robyr D, Kurdistani SK, Grunstein M (2003) Analysis of genome-wide histone . Methods In Enzymology 2003; 376: 289-304.
Mellone BG, Ball L, Suka N, Grunstein MR, Partridge JF, Allshire RC Centromere silencing and function in fission yeast is governed by the amino terminus of histone H3. Current biology : CB. . 2003; 13(20): 1748-57.
Robyr D, Grunstein M Genomewide histone acetylation microarrays. Methods (San Diego, Calif.) . 2003; 31(1): 83-9.
Kurdistani SK, Grunstein M Histone acetylation and deacetylation in yeast. Nat Rev Mol Cell Biol. 2003; 4(4): 276-84.
Thompson JS, Snow ML, Giles S, McPherson LE, Grunstein M Identification of a functional domain within the essential core of histone H3 that is required for telomeric and HM silencing in Saccharomyces cerevisiae. Genetics. . 2003; 163(1): 447-52.
Kurdistani SK, Grunstein M In vivo protein-protein and protein-DNA crosslinking for genomewide binding microarray. Methods (San Diego, Calif.) . 2003; 31(1): 90-5.
Carmen AA, Milne L, Grunstein M Acetylation of the yeast histone H4 N terminus regulates its binding to heterochromatin protein SIR3. The Journal of biological chemistry. . 2002; 277(7): 4778-81.
Kurdistani SK, Robyr D, Tavazoie S, Grunstein M Genome-wide binding map of the histone deacetylase Rpd3 in yeast. Nature genetics. . 2002; 31(3): 248-54.
Vogelauer M, Rubbi L, Lucas I, Brewer BJ, Grunstein M Histone acetylation regulates the time of replication origin firing. Molecular cell. . 2002; 10(5): 1223-33.
Robyr D, Suka Y, Xenarios I, Kurdistani SK, Wang A, Suka N, Grunstein M Microarray deacetylation maps determine genome-wide functions for yeast histone deacetylases. Cell. . 2002; 109(4): 437-46.
Luo K, Vega-Palas MA, Grunstein M Rap1-Sir4 binding independent of other Sir, yKu, or histone interactions initiates the assembly of telomeric heterochromatin in yeast. Genes & development. . 2002; 16(12): 1528-39.
Wang A, Kurdistani SK, Grunstein M Requirement of Hos2 histone deacetylase for gene activity in yeast. Science. . 2002; 298(5597): 1412-4.
Suka N, Luo K, Grunstein M Sir2p and Sas2p opposingly regulate acetylation of yeast histone H4 lysine16 and spreading of heterochromatin. Nature genetics. . 2002; 32(3): 378-83.
Kristjuhan A, Walker J, Suka N, Grunstein M, Roberts D, Cairns BR, Svejstrup JQ Transcriptional inhibition of genes with severe histone h3 hypoacetylation in the coding region. Molecular cell. . 2002; 10(4): 925-33.
Wu J, Carmen AA, Kobayashi R, Suka N, Grunstein M HDA2 and HDA3 are related proteins that interact with and are essential for the activity of the yeast histone deacetylase HDA1. Proceedings of the National Academy of Sciences of the United States of America. . 2001; 98(8): 4391-6.
Suka N, Suka Y, Carmen AA, Wu J, Grunstein M Highly specific antibodies determine histone acetylation site usage in yeast heterochromatin and euchromatin. Molecular cell. . 2001; 8(2): 473-9.
Wu J, Suka N, Carlson M, Grunstein M TUP1 utilizes histone H3/H2B-specific HDA1 deacetylase to repress gene activity in yeast. Molecular cell. . 2001; 7(1): 117-26.
Wu J, Grunstein M 25 years after the nucleosome model: chromatin modifications. Trends in biochemical sciences. . 2000; 25(12): 619-23.
Clark WR, Grunstein M Are we hardwired? The role of genes in human behavior. Oxford Univ. Press. N.Y., N.Y. 2000; 1st Edition: .
Vogelauer M, Wu J, Suka N, Grunstein M Global histone acetylation and deacetylation in yeast. Nature 2000; 408: 495-498.
Free A, Grunstein M, Bird A, Vogelauer M Histone deacetylation: Repressor Mechanisms. Chromatin Structure and Gene Expression. Frontiers in Molecular Biology 2000; 2nd Edition: .
Wyrick JJ, Holstege FC, Jennings EG, Causton HC, Shore D, Grunstein M, Lander ES, Young RA Chromosomal landscape of nucleosome-dependent gene expression and silencing in yeast. Nature. . 1999; 402(6760): 418-21.
Kadonaga JT, Grunstein M Chromosomes and Expression Mechanisms. Current Opinion in Genetics and Development 1999; Vol. 9 no. 2, April: .
Martin SG, Laroche T, Suka N, Grunstein M, Gasser SM Relocalization of telomeric Ku and SIR proteins in response to DNA strand breaks in yeast. Cell. . 1999; 97(5): 621-33.
Carmen AA, Griffin PR, Calaycay JR, Suka N, Grunstein M Yeast HOS3 forms a novel TSA-insensitive homodimer with intrinsic catalytic activity. Proc. Nat. Acad. Sci. USA 1999; 96: 12356-12361.
Ma X-J, Wu J, Altheim A, Schultz MC, Grunstein M Deposition-related sites K5/K12 in histone H4 are not required for nucleosome deposition in yeast. Proc. Nat. Acad. Sci. USA 1998; 95: 6693-6698.
Rundlett SE, Carmen AA, Suka N, Turner BM, Grunstein M Transcriptional repression by UME6 involves deacetylation of lysine 5 of histone H4 by RPD3. Nature. . 1998; 392(6678): 831-5.
Grunstein M Yeast heterochromatin: regulation of its assembly and inheritance by histones. Cell. . 1998; 93(3): 325-8.
Grunstein M Histone acetylation in chromatin structure and transcription. Nature 1997; 389: 349-352.
Strahl-Bolsinger S, Hecht A, Luo K, Grunstein M SIR2 and SIR4 interactions differ in core and extended telomeric heterochromatin in yeast. Genes & development. . 1997; 11(1): 83-93.
Ma X, Lu Q, Grunstein M A search for proteins that interact genetically with histone H3 and H4 N-termini uncovers novel regulators of the Swe 1 kinase in Saccharomyces cerevisiae. Genes and Development 1996; 10: 1327-1340.
Lenfant F, Mann RK, Thomsen B, Ling X, Grunstein M All four core histone N-termini contain sequences required for the repression of basal transcription in yeast. The EMBO journal. . 1996; 15(15): 3974-85.
Carmen AA, Rundlett SE, Grunstein M HDA1 and HDA3 are components of a yeast histone deacetylase (HDA) complex. The Journal of biological chemistry. . 1996; 271(26): 15837-44.
Rundlett SE, Carmen AA, Kobayashi R, Bavykin S, Turner BM, Grunstein M HDA1 and RPD3 are members of distinct yeast histone deacetylase complexes that regulate silencing and transcription. Proceedings of the National Academy of Sciences of the United States of America. . 1996; 93(25): 14503-8.
Hecht A, Strahl-Bolsinger S, Grunstein M Spreading of transcriptional repressor SIR3 from telomeric heterochromatin. Nature. . 1996; 383(6595): 92-6.
Ling X, Harkness TAA, Schultz MC, Fisher-Adams G, Grunstein M Yeast histone H3 and H4 N-termini are important for nucleosome assembly in vivo and in vitro. Genes and Development 1996; 10: 686-699.
Hecht A, Laroche T, Strahl-Bolsinger S, Gasser SM, Grunstein M Histone H3 and H4 N-termini interact with SIR3 and SIR4 proteins: a molecular model for the formation of heterochromatin in yeast. Cell. . 1995; 80(4): 583-92.
Wan JS, Mann RK, Grunstein M Yeast histone H3 and H4 N termini function through different GAL1 regulatory elements to repress and activate transcription. Proceedings of the National Academy of Sciences of the United States of America. . 1995; 92(12): 5664-8.
Fisher-Adams G, Grunstein M Yeast histone H4 and H3 N-termini have different effects on the chromatin structure of the GAL1 promoter. The EMBO journal. . 1995; 14(7): 1468-77.
Thompson JS, Ling X, Grunstein M Histone H3 amino terminus is required for telomeric and silent mating locus repression in yeast. Nature. . 1994; 369(6477): 245-7.
Mann RK, Grunstein M Histone H3 N-terminal mutations allow hyperactivation of the yeast GAL1 gene in vivo. The EMBO journal. . 1992; 11(9): 3297-306.
Grunstein M Histones as regulators of genes. Scientific American 1992; 267: 68-74.
Johnson LM, Fisher-Adams G, Grunstein M Identification of a non-basic domain in the histone H4 N-terminus required for repression of the yeast silent mating loci. The EMBO journal. . 1992; 11(6): 2201-9.
Durrin LK, Mann RK, Kayne PS, Grunstein M Yeast histone H4 N-terminal sequence is required for promoter activation in vivo. Cell. . 1991; 65(6): 1023-31.
Johnson LM, Kayne PS, Kahn ES, Grunstein M Genetic evidence for an interaction between SIR3 and histone H4 in the repression of the silent mating loci in Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the United States of America. . 1990; 87(16): 6286-90.
Grunstein M Histone function in transcription. Annual Reviews of Cell Biology 1990; 6: 643-678.
Han M, Kim UJ, Kayne P, Grunstein M Depletion of histone H4 and nucleosomes activates the PHO5 gene in Saccharomyces cerevisiae. The EMBO journal. . 1988; 7(7): 2221-8.
Kayne PS, Kim UJ, Han M, Mullen JR, Yoshizaki F, Grunstein M Extremely conserved histone H4 N terminus is dispensable for growth but essential for repressing the silent mating loci in yeast. Cell. . 1988; 55(1): 27-39.
Han M, Grunstein M Nucleosome loss activates yeast downstream promoters in vivo. Cell. . 1988; 55(6): 1137-45.
Han M, Chang M, Kim UJ, Grunstein M Histone H2B repression causes cell-cycle-specific arrest in yeast: effects on chromosomal segregation, replication, and transcription. Cell. . 1987; 48(4): 589-97.
Schuster T, Han M, Grunstein M Yeast histone H2A and H2B amino termini have interchangeable functions. Cell. . 1986; 45(3): 445-51.
Travis GH, Colavito-Shepanski M, Grunstein M Extensive purification and characterization of chromatin-bound histone acetyltransferase from Saccharomyces cerevisiae. The Journal of biological chemistry. . 1984; 259(23): 14406-12.
Wallis JW, Rykowski M, Grunstein M Yeast histone H2B containing large amino terminus deletions can function in vivo. Cell. . 1983; 35(3 Pt 2): 711-9.
Rykowski MC, Wallis JW, Choe J, Grunstein M Histone H2B subtypes are dispensable during the yeast cell cycle. Cell. . 1981; 25(2): 477-87.
Wallis JW, Hereford L, Grunstein M Histone H2B genes of yeast encode two different proteins. Cell. . 1980; 22(3): 799-805.
Grunstein M, Hogness DS Colony hybridization: a method for the isolation of cloned DNAs that contain a specific gene. Proceedings of the National Academy of Sciences of the United States of America. . 1975; 72(10): 3961-5.