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 #
5P01GM088297-05
Application #
8650893
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
2014-04-01
Budget End
2015-03-31
Support Year
5
Fiscal Year
2014
Total Cost
$1,489,836
Indirect Cost
$534,687
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
Jin, Liang; Zhang, Kai; Sternglanz, Rolf et al. (2017) Predicted RNA Binding Proteins Pes4 and Mip6 Regulate mRNA Levels, Translation, and Localization during Sporulation in Budding Yeast. Mol Cell Biol 37:
Zhou, Sai; Sternglanz, Rolf; Neiman, Aaron M (2017) Developmentally regulated internal transcription initiation during meiosis in budding yeast. PLoS One 12:e0188001
Mukherjee, Kaustav; Gardin, Justin; Futcher, Bruce et al. (2016) Relative contributions of the structural and catalytic roles of Rrp6 in exosomal degradation of individual mRNAs. RNA 22:1311-9
Callender, Tracy L; Laureau, Raphaelle; Wan, Lihong et al. (2016) Mek1 Down Regulates Rad51 Activity during Yeast Meiosis by Phosphorylation of Hed1. PLoS Genet 12:e1006226
Jin, Liang; Neiman, Aaron M (2016) Post-transcriptional regulation in budding yeast meiosis. Curr Genet 62:313-5
Chen, Xiangyu; Suhandynata, Ray T; Sandhu, Rima et al. (2015) Phosphorylation of the Synaptonemal Complex Protein Zip1 Regulates the Crossover/Noncrossover Decision during Yeast Meiosis. PLoS Biol 13:e1002329
Lin, Ching-Jung; Smibert, Peter; Zhao, Xiaoyu et al. (2015) An extensive allelic series of Drosophila kae1 mutants reveals diverse and tissue-specific requirements for t6A biogenesis. RNA 21:2103-18
Garg, Angad; Futcher, Bruce; Leatherwood, Janet (2015) A new transcription factor for mitosis: in Schizosaccharomyces pombe, the RFX transcription factor Sak1 works with forkhead factors to regulate mitotic expression. Nucleic Acids Res 43:6874-88
Jin, Liang; Zhang, Kai; Xu, Yifeng et al. (2015) Sequestration of mRNAs Modulates the Timing of Translation during Meiosis in Budding Yeast. Mol Cell Biol 35:3448-58
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

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