Multivalent binding of p53 to the STAGA complex mediates coactivator recruitment after UV damage.

Abstract:

:The recruitment of transcriptional coactivators, including histone modifying enzymes, is an important step in transcription regulation. A typical activator is thought to interact with several cofactors, presumably in a sequential manner. The common use of several cofactors raises the question of how activators achieve both cofactor selectivity and diversity. Human STAGA is a multiprotein complex with the acetyltransferase GCN5L as the catalytic subunit. Here, we first show, through RNA interference-mediated knock-down and chromatin immunoprecipitation assays, that GCN5 plays a role in p53-dependent gene activation. We then employ p53 mutagenesis, in vitro binding, protein-protein cross-linking, and chromatin immunoprecipitation assays to establish a novel role for the second p53 activation subdomain (AD2) in STAGA recruitment and, further, to demonstrate that optimal binding of STAGA to p53 involves interactions of STAGA subunits TAF9, GCN5, and ADA2b, respectively, with AD1, AD2, and carboxy-terminal domains of p53. These results provide concrete evidence for mediation of transcription factor binding to coactivator complexes through multiple interactions. Based on our data, we propose a cooperative and modular binding mode for the recruitment of coactivator complexes to promoters.

journal_name

Mol Cell Biol

authors

Gamper AM,Roeder RG

doi

10.1128/MCB.01461-07

subject

Has Abstract

pub_date

2008-04-01 00:00:00

pages

2517-27

issue

8

eissn

0270-7306

issn

1098-5549

pii

MCB.01461-07

journal_volume

28

pub_type

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