Significant advances have been made in understanding the regulation of eukaryotic gene expression in the past years. The complexity and intricacy inherent in RNA polymerase II-mediated transcription is manifested by the large number of components that facilitate and regulate this process. The advances in this field have been buttressed by convergence of yeast genetics and biochemistry, the development of advanced technologies that expedite protein isolation and identification, the exploitation of structural biology and additional resources gained from the genome project, such as genomics and proteomics. The establishment of well-defined transcription assays has expedited the characterization of the functional role(s) of many of these factors. We are now in a position to analyze the dynamic relationships of these components at the protein:protein and protein:DNA levels. To this end, this proposal contains detailed analyses of several stages of the transcription process including studies of how specific factors modify each stage. This represents an expansion of the ongoing studies in my laboratory regarding the identification and functional role(s) of each of the key components in transcription. As well, this proposal now tackles the regulation of each of the activities of these components. This will define the precise steps and factors that are targeted by moderators that evolved to control the transcription process. Finally, this proposal includes studies of the transcription cycle using natural promoters with natural activators within the context of chromatin. These studies will complement the proposed functional analyses by defining the spacial interrelationships of the transcription factors with respect to each other and with respect to their access to transcription moderators. Our studies on promoter recognition and activation by the general transcription factors of the RNA polymerase II transcription system have broad implications for the mechanism of RNA synthesis in general and will provide the basis for understanding how specific gene transcription factors can modify the transcriptional activity of a particular gene or a set of genes. It is likely that these studies will yield basic principles from which the regulatory mechanisms of class II gene expression can be discerned at the molecular level.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37GM037120-27
Application #
8247815
Study Section
Special Emphasis Panel (NSS)
Program Officer
Sledjeski, Darren D
Project Start
1986-11-01
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
27
Fiscal Year
2012
Total Cost
$495,952
Indirect Cost
$203,355
Name
New York University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Lecona, Emilio; Narendra, Varun; Reinberg, Danny (2015) USP7 cooperates with SCML2 to regulate the activity of PRC1. Mol Cell Biol 35:1157-68
Jacob, Yannick; Bergamin, Elisa; Donoghue, Mark T A et al. (2014) Selective methylation of histone H3 variant H3.1 regulates heterochromatin replication. Science 343:1249-53
Kaneko, Syuzo; Bonasio, Roberto; Saldaña-Meyer, Ricardo et al. (2014) Interactions between JARID2 and noncoding RNAs regulate PRC2 recruitment to chromatin. Mol Cell 53:290-300
Campos, Eric I; Stafford, James M; Reinberg, Danny (2014) Epigenetic inheritance: histone bookmarks across generations. Trends Cell Biol 24:664-74
Lecona, Emilio; Rojas, Luis Alejandro; Bonasio, Roberto et al. (2013) Polycomb protein SCML2 regulates the cell cycle by binding and modulating CDK/CYCLIN/p21 complexes. PLoS Biol 11:e1001737
Serrano, Lourdes; Martínez-Redondo, Paloma; Marazuela-Duque, Anna et al. (2013) The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation. Genes Dev 27:639-53
Voigt, Philipp; Tee, Wee-Wei; Reinberg, Danny (2013) A double take on bivalent promoters. Genes Dev 27:1318-38
Hsieh, Fu-Kai; Kulaeva, Olga I; Patel, Smita S et al. (2013) Histone chaperone FACT action during transcription through chromatin by RNA polymerase II. Proc Natl Acad Sci U S A 110:7654-9
Beck, David B; Oda, Hisanobu; Shen, Steven S et al. (2012) PR-Set7 and H4K20me1: at the crossroads of genome integrity, cell cycle, chromosome condensation, and transcription. Genes Dev 26:325-37
Dhar, Shilpa S; Lee, Sung-Hun; Kan, Pu-Yeh et al. (2012) Trans-tail regulation of MLL4-catalyzed H3K4 methylation by H4R3 symmetric dimethylation is mediated by a tandem PHD of MLL4. Genes Dev 26:2749-62

Showing the most recent 10 out of 108 publications