Abstract

The heat shock genes of Drosphila melanogaster constitute a technically well-suited model system for defining general principles of gene regulation in animal cells. The heat shock genes occupy several chromosomal loci that are coodinately activated by heat and a variety of other treatments. The objectives of this proposal are to identify DNA sequences and proteins involved in regulatory interactions at these loci, and to study the correspondence of these interactions to accompanying alterations in chromosome structure. To accomplish these objectives, four interrelated analyses are to be executed, all using cloned DNA segments: (1) sequencing DNA at sites of transcription initiation of a select set of loci to identify conserved elements, (2) testing the affect of in vitro-induced mutations of such conserved sequences on transcription initiation, (3) mapping specific protein-DNA interactions utilizing a newly devised chemical-crosslinking, gene-purification approach, (4) mapping alterations in chromatin structure which accompany gene activation by partial DNAseI digestion, followed by hybridization with specific cloned DNAs.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM025232-08
Application #
3272843
Study Section
Genetics Study Section (GEN)
Project Start
1978-04-01
Project End
1986-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
8
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Cornell University
Department
Type
Schools of Arts and Sciences
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850

  Publications

Booth, Gregory T; Parua, Pabitra K; Sansó, Miriam et al. (2018) Cdk9 regulates a promoter-proximal checkpoint to modulate RNA polymerase II elongation rate in fission yeast. Nat Commun 9:543
Tome, Jacob M; Tippens, Nathaniel D; Lis, John T (2018) Single-molecule nascent RNA sequencing identifies regulatory domain architecture at promoters and enhancers. Nat Genet 50:1533-1541
Chu, Tinyi; Rice, Edward J; Booth, Gregory T et al. (2018) Chromatin run-on and sequencing maps the transcriptional regulatory landscape of glioblastoma multiforme. Nat Genet 50:1553-1564
Vihervaara, Anniina; Duarte, Fabiana M; Lis, John T (2018) Molecular mechanisms driving transcriptional stress responses. Nat Rev Genet 19:385-397
Parua, Pabitra K; Booth, Gregory T; Sansó, Miriam et al. (2018) A Cdk9-PP1 switch regulates the elongation-termination transition of RNA polymerase II. Nature 558:460-464
Mahat, Dig B; Lis, John T (2017) Use of conditioned media is critical for studies of regulation in response to rapid heat shock. Cell Stress Chaperones 22:155-162
Boija, Ann; Mahat, Dig Bijay; Zare, Aman et al. (2017) CBP Regulates Recruitment and Release of Promoter-Proximal RNA Polymerase II. Mol Cell 68:491-503.e5
Vihervaara, Anniina; Mahat, Dig Bijay; Guertin, Michael J et al. (2017) Transcriptional response to stress is pre-wired by promoter and enhancer architecture. Nat Commun 8:255
Watters, Kyle E; Strobel, Eric J; Yu, Angela M et al. (2016) Cotranscriptional folding of a riboswitch at nucleotide resolution. Nat Struct Mol Biol 23:1124-1131
Booth, Gregory T; Wang, Isabel X; Cheung, Vivian G et al. (2016) Divergence of a conserved elongation factor and transcription regulation in budding and fission yeast. Genome Res 26:799-811

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