The long term goal of this research is to understand the role of histone modifications such as acetylation and methylation and their effect on chromosome function, using the widely-studied yeast, Saccharomyces cerevisiae, to study these processes. In particular this grant will focus on the effect of histone modifications on transcription. The grant has 3 aims. The first one (1) focuses on how the cyclin-dependent kinase Bur1 controls methylation of histone H3 lysine 36 by the histone methylase Set2. Set2 is known to be associated with RNA polymerase II during transcriptional elongation, and we think that Bur1 controls a crucial step in the elongation process, acting through Set2.
The second aim i s concerned with using mass spectroscopy on highly purified yeast histones H2A and H2B to identify modifications such as acetylation and methylation of lysine residues. Once specific modified residues have been identified, the effects of mutating them will be investigated and the enzymes responsible for the modifications will be determined.
The third aim i s to study Spt10, a protein known to be important for transcription of histone genes and perhaps other genes. Spt10 is thought to be an N-acetyltransferase based on its sequence, but its substrate may not be histones. A novel method involving peptide libraries will be used to identify the protein(s) that Spt10 acetylates. Since histones and their modifications are highly conserved from yeast to humans, as is the process of gene expression, these studies will lead to a greater understanding of fundamental functions of chromosomes in human cells.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Molecular Genetics B Study Section (MGB)
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Carter, Anthony D
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State University New York Stony Brook
Schools of Medicine
Stony Brook
United States
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Sampath, Vinaya; Liu, Bingsheng; Tafrov, Stefan et al. (2013) Biochemical characterization of Hpa2 and Hpa3, two small closely related acetyltransferases from Saccharomyces cerevisiae. J Biol Chem 288:21506-13
Yuan, Hua; Rossetto, Dorine; Mellert, Hestia et al. (2012) MYST protein acetyltransferase activity requires active site lysine autoacetylation. EMBO J 31:58-70
Yu, Yao; Srinivasan, Madhusudhan; Nakanishi, Shima et al. (2011) A conserved patch near the C terminus of histone H4 is required for genome stability in budding yeast. Mol Cell Biol 31:2311-25
Srinivasan, Madhusudhan; Mehta, Preeti; Yu, Yao et al. (2011) The highly conserved KEOPS/EKC complex is essential for a universal tRNA modification, t6A. EMBO J 30:873-81
Ren, Jie; Wang, Chia-Lin; Sternglanz, Rolf (2010) Promoter strength influences the S phase requirement for establishment of silencing at the Saccharomyces cerevisiae silent mating type Loci. Genetics 186:551-60
Yu, Yao; Neiman, Aaron M; Sternglanz, Rolf (2010) The JmjC domain of Gis1 is dispensable for transcriptional activation. FEMS Yeast Res 10:793-801
Kumar, P Rajesh; Yu, Yao; Sternglanz, Rolf et al. (2008) NADP regulates the yeast GAL induction system. Science 319:1090-2
Chu, Yaya; Sutton, Ann; Sternglanz, Rolf et al. (2006) The BUR1 cyclin-dependent protein kinase is required for the normal pattern of histone methylation by SET2. Mol Cell Biol 26:3029-38
Hess, David; Liu, Bingsheng; Roan, Nadia R et al. (2004) Spt10-dependent transcriptional activation in Saccharomyces cerevisiae requires both the Spt10 acetyltransferase domain and Spt21. Mol Cell Biol 24:135-43
Min, J; Landry, J; Sternglanz, R et al. (2001) Crystal structure of a SIR2 homolog-NAD complex. Cell 105:269-79

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