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  • The EMBO Journal (2003) 22, 2146 - 2155
  • doi:10.1093/emboj/cdg219

A role for cofactor–cofactor and cofactor–histone interactions in targeting p300, SWI/SNF and Mediator for transcription

Zhi-Qing Huang1, Jiwen Li1, Laurent M. Sachs2, Philip A. Cole3 and Jiemin Wong1

  1. Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
  2. Département Régulation, Développement et Diversité Moléculaire, UMS 501 MNHN, UMR CNRS 8572, 7 rue Cuvier, 75231 Paris cedex 05, France
  3. Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

Correspondence to:

Jiemin Wong, E-mail: jwong@bcm.tmc.edu

Received 12 December 2002; Accepted 13 March 2003; Revised 5 March 2003

Transcriptional activation from chromatin by nuclear receptors (NRs) requires multiple cofactors including CBP/p300, SWI/SNF and Mediator. How NRs recruit these multiple cofactors is not clear. Here we show that activation by androgen receptor and thyroid hormone receptor is associated with the promoter targeting of SRC family members, p300, SWI/SNF and the Mediator complex. We show that recruitment of SWI/SNF leads to chromatin remodeling with altered DNA topology, and that both SWI/SNF and p300 histone acetylase activity are required for hormone-dependent activation. Importantly, we show that both the SWI/SNF and Mediator complexes can be targeted to chromatin by p300, which itself is recruited through interaction with SRC coactivators. Furthermore, histone acetylation by CBP/p300 facilitates the recruitment of SWI/SNF and Mediator. Thus, our data indicate that multiple cofactors required for activation are not all recruited through their direct interactions with NRs and underscore a role of cofactor–cofactor interaction and histone modification in coordinating the recruitment of multiple cofactors.

  • Keywords:

    • chromatin remodeling,
    • cofactor recruitment,
    • NRs