Knowledge of the roles of transcription activators and certain components of the transcription apparatus is now available for a few selected genes, but their roles are not known throughout the genome of any organism. We propose to explore the genome-wide location and function of activators and components of the transcription apparatus in yeast cells by using a combination of genetic, biochemical, genomic and computational tools. We will test several models that have been proposed to apply a global gene regulation but which have yet to be examined experimentally. To accomplish these goals, the four specific aims of this proposal are: 1) to identify the genomic sites bound by the 180 putative transcription activators in yeast under multiple growth conditions; 2) to determine the location and functional requirement for """"""""initiation"""""""" factors globally; 3) to determine the location and functional requirement for """"""""elongation"""""""" factors globally; and 4) to evaluate the relationship between location and function for selected factors during the response to a change in growth environment. The results of this investigation should provide a foundation for all investigators interested in further study of the mechanisms involved in global gene regulation. The health relatedness of this project devices from its contribution to the understanding of the fundamental mechanisms that control gene expression.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM034365-19
Application #
6628799
Study Section
Genetics Study Section (GEN)
Program Officer
Tompkins, Laurie
Project Start
1984-12-01
Project End
2005-01-31
Budget Start
2003-02-01
Budget End
2004-01-31
Support Year
19
Fiscal Year
2003
Total Cost
$348,750
Indirect Cost
Name
Whitehead Institute for Biomedical Research
Department
Type
DUNS #
120989983
City
Cambridge
State
MA
Country
United States
Zip Code
02142
Ng, Huck Hui; Robert, Francois; Young, Richard A et al. (2003) Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. Mol Cell 11:709-19
Wyrick, J J; Aparicio, J G; Chen, T et al. (2001) Genome-wide distribution of ORC and MCM proteins in S. cerevisiae: high-resolution mapping of replication origins. Science 294:2357-60
Geisberg, J V; Holstege, F C; Young, R A et al. (2001) Yeast NC2 associates with the RNA polymerase II preinitiation complex and selectively affects transcription in vivo. Mol Cell Biol 21:2736-42
Robertson, L S; Causton, H C; Young, R A et al. (2000) The yeast A kinases differentially regulate iron uptake and respiratory function. Proc Natl Acad Sci U S A 97:5984-8
Kimmelman, J; Kaldis, P; Hengartner, C J et al. (1999) Activating phosphorylation of the Kin28p subunit of yeast TFIIH by Cak1p. Mol Cell Biol 19:4774-87
Hengartner, C J; Myer, V E; Liao, S M et al. (1998) Temporal regulation of RNA polymerase II by Srb10 and Kin28 cyclin-dependent kinases. Mol Cell 2:43-53
Woychik, N A; McKune, K; Lane, W S et al. (1993) Yeast RNA polymerase II subunit RPB11 is related to a subunit shared by RNA polymerase I and III. Gene Expr 3:77-82
McKune, K; Richards, K L; Edwards, A M et al. (1993) RPB7, one of two dissociable subunits of yeast RNA polymerase II, is essential for cell viability. Yeast 9:295-9
Choder, M; Young, R A (1993) A portion of RNA polymerase II molecules has a component essential for stress responses and stress survival. Mol Cell Biol 13:6984-91
Woychik, N A; Young, R A (1992) Genes encoding transcription factor IIIA and the RNA polymerase common subunit RPB6 are divergently transcribed in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 89:3999-4003

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