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This version published online on November 22, 2006
Molecular Endocrinology, doi:10.1210/me.2006-0361
A more recent version of this article appeared on February 1, 2007
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Submitted on August 30, 2006
Accepted on November 13, 2006

Coregulator Exchange and Sphingosine-Sensitive Cooperativity of Steroidogenic Factor-1, GCN5, p54, and p160 Coactivators Regulate cAMP-Dependent CYP17 Transcription Rate

Eric B. Dammer, Adam Leon, and Marion B. Sewer*

School of Biology, Parker H. Petit Institute for Bioengineering & Biosciences, Georgia Institute of Technology, Atlanta, GA 30332-0230

* To whom correspondence should be addressed. E-mail: marion.sewer{at}biology.gatech.edu.

Transcription of the CYP17 gene is regulated by cAMP-dependent binding of steroidogenic factor-1 (SF-1) to its promoter in the adrenal cortex. Using temporal chromatin immunoprecipitation and mammalian two hybrid experiments, we establish the reciprocal presence of coactivators [general control nonderepressed (GCN5), cAMP response element binding protein-binding protein (CBP), p300, p300/CBP associated factor (P/CAF), p160s, polypyrimidine tract associated splicing factor (PSF), and p54nrb], corepressors [class I histone deacetylases (HDACs), receptor interacting protein (RIP140), nuclear receptor corepressor (NCoR), and Sin3A], and SWI/SNF and ISWI chromatin remodeling ATPases on the CYP17 promoter during transcription cycles in the H295R adrenocortical cell line. A ternary GCN5/SRC-1/SF-1 complex forms on the CYP17 promoter with cAMP-dependence within 30 min of cAMP stimulation, and corresponds with SWI/SNF chromatin remodeling. This complex is sensitive to the SF-1 antagonist sphingosine (Sph) and results in decreased transcription of CYP17. GCN5 acetyltransferase activity and carboxy terminus binding proteins (CtBP) alternatively mediate disassembly of the complex. This work establishes the temporal order of cAMP-induced events on the promoter of a key steroidogenic gene during SF-1-mediated transcription.

NURSA Molecule Pages Link:

Nuclear Receptors:   SF-1  |  LRH-1
Coregulators:   p54nrb  |  RIP140  |  P/CAF  |  PSF  |  Sin3A  |  BRM  |  BRG1  |  CBP  |  CtBP1  |  p300  |  HDAC1  |  HDAC2  |  HDAC3  |  SRC-1  |  GRIP1  |  AIB1  |  NCOR  |  SMRT



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