Abstract

CBP/p300 are important coactivators for several transcription factors including CREB, nuclear hormone receptors, NF- B and p53. Recent experiments suggest that CBP/p300 mediate gene activation through effects on chromatin remodeling, but interactions with basal transcription factors have also been proposed. To analyze CBP transcription activation, we have utilized an in vitro transcription assay that allows the analysis of transcription initiation and reinitiation in the absence of chromatin effects. Addition of Tax and a N-terminal fragment of CBP (amino acids 1-682) to the in vitro transcription reactions increased both full-length and shorter transcripts resulting from initiation and reinitiation. A CBP deletion mutant lacking the N-terminal activation domain was inactive. Analysis of the interaction of Tax with full-length endogenous CBP indicates that a transcriptionally active complex of Tax/CBP/RNA pol II can be immunoprecipitated from cell extracts. We propose that CBP activates transcription in vivo not only by loosening chromatin structure by its histone acetylase function, but also by directly promoting transcription initiation and reinitiation through Tax-responsive CREB binding.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC005254-16
Application #
6160879
Study Section
Special Emphasis Panel (LRBG)
Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

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Chevalier, Sebastien Alain; Ko, Nga Ling; Calattini, Sara et al. (2008) Construction and characterization of a human T-cell lymphotropic virus type 3 infectious molecular clone. J Virol 82:6747-52
Cho, Won-Kyung; Zhou, Meisheng; Jang, Moon Kyoo et al. (2007) Modulation of the Brd4/P-TEFb interaction by the human T-lymphotropic virus type 1 tax protein. J Virol 81:11179-86
Zhou, Meisheng; Lu, Hanxin; Park, Hyeon et al. (2006) Tax interacts with P-TEFb in a novel manner to stimulate human T-lymphotropic virus type 1 transcription. J Virol 80:4781-91
Gegonne, Anne; Weissman, Jocelyn D; Zhou, Meisheng et al. (2006) TAF7: a possible transcription initiation check-point regulator. Proc Natl Acad Sci U S A 103:602-7
Ohyama, Manabu; Terunuma, Atsushi; Tock, Christine L et al. (2006) Characterization and isolation of stem cell-enriched human hair follicle bulge cells. J Clin Invest 116:249-60
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Minn, Alexandra H; Pise-Masison, Cynthia A; Radonovich, Michael et al. (2005) Gene expression profiling in INS-1 cells overexpressing thioredoxin-interacting protein. Biochem Biophys Res Commun 336:770-8
Jang, Moon Kyoo; Mochizuki, Kazuki; Zhou, Meisheng et al. (2005) The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription. Mol Cell 19:523-34

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