Overview - This Program Project explores the idea that when a cell enters the meiotic state, it undergoes a radical re-wiring of gene expression programs. A more conservative view was that meiotic cells are broadly similar to vegetative cells, but express additional, meiosis-specific genes. We explore a more radical view in which even genes that are expressed in both vegetative and meiotic cells are expressed in a different fashion, regulated by different transcription factors in meiotic cells. Furthermore meiotic cells may use a larger repertoire of mechanisms to control gene expression than vegetative cells. In short, when cells differentiate from the vegetative state into the meiotic state, their gene expression programs are extensively re-wired. We will study this re-wiring, and novel, meiosis-specific regulatory mechanisms. The first three projects use S. cerevisiae, and focus on regulatory mechanisms in early, middle, and late meiosis, respectively. The fourth project uses S. pombe, and focuses on novel meiotic regulatory mechanisms. Projects. 1. Wiring of Gene Expression in the Early Meiotic Program (Dr. Futcher) 2. Meiotic Cdc7 switches and substrates, and the activation of Ndt80 (Dr. Hollingsworth) 3. Histone modification and Chromatin Switches in the Meiotic state (Drs. Neiman and Sternglanz) 4. Novel mechanisms of gene regulation in Meiosis: Antisense RNAs and RNA processing. (Dr. Leatherwood) The research Projects will be supported by a Microarray Core Facility, which will play a crucial role in all four projects.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM088297-04
Application #
8451428
Study Section
Special Emphasis Panel (ZRG1-CB-Q (40))
Program Officer
Sledjeski, Darren D
Project Start
2010-04-01
Project End
2015-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
4
Fiscal Year
2013
Total Cost
$1,437,692
Indirect Cost
$515,973
Name
State University New York Stony Brook
Department
Genetics
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Ucisik-Akkaya, Esma; Leatherwood, Janet K; Neiman, Aaron M (2014) A genome-wide screen for sporulation-defective mutants in Schizosaccharomyces pombe. G3 (Bethesda) 4:1173-82
Berchowitz, Luke E; Gajadhar, Aaron S; van Werven, Folkert J et al. (2013) A developmentally regulated translational control pathway establishes the meiotic chromosome segregation pattern. Genes Dev 27:2147-63
Lo, Hsiao-Chi; Kunz, Ryan C; Chen, Xiangyu et al. (2012) Cdc7-Dbf4 is a gene-specific regulator of meiotic transcription in yeast. Mol Cell Biol 32:541-57
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
Neiman, Aaron M (2011) Sporulation in the budding yeast Saccharomyces cerevisiae. Genetics 189:737-65
Chen, Huei-Mei; Neiman, Aaron M (2011) A conserved regulatory role for antisense RNA in meiotic gene expression in yeast. Curr Opin Microbiol 14:655-9
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
Yu, Yao; Neiman, Aaron M; Sternglanz, Rolf (2010) The JmjC domain of Gis1 is dispensable for transcriptional activation. FEMS Yeast Res 10:793-801