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Steroid receptor coactivator-1 is a histone acetyltransferase

Nature volume 389, pages 194–198 (1997)Cite this article

Abstract

Steroid receptors and coactivator proteins are thought to stimulate gene expression by facilitating the assembly of basal transcription factors into a stable preinitiation complex1. What is not clear, however, is how these transcription factors gain access to transcriptionally repressed chromatin to modulate the transactivation of specific gene networks in vivo. The available evidence indicates that acetylation of chromatin in vivo is coupled to transcription and that specific histone acetyltransferases (HATs)target histones bound to DNA and overcome the inhibitory effect of chromatin on gene expression2,3,4. The steroid-receptor coactivator SRC-1 is a coactivator for many members of the steroid-hormone receptor superfamily of ligand-inducible transcription factors5. Here we show that SRC-1 possesses intrinsic histone acetyltransferase activity and that it also interacts with another HAT, p300/CBP-associated factor (PCAF). The HAT activity of SRC-1 maps to its carboxy-terminal region and is primarily specific for histones H3 and H4. Acetylation by SRC-1 and PCAF of histones bound at specific promoters may result from ligand binding to steroid receptors and could be a mechanism by which the activation functions of steroid receptors and associated coactivators enhance formation of a stable preinitiation complex, thereby increasing transcription of specific genes from transcriptionally repressed chromatin templates.

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Figure 1: a, SRC-1 antibodies immunoprecipitate HAT activity.
Figure 2: a, Representation of SRC-1 shows the position of domains for the basic helix–loop–helix (bHLH), Per-Arnt-Sim (PAS), serine/threonine(S/T)-rich, glutamine(Q)/rich and dominant-negative (DN) regions5,18.
Figure 3: a, SRC-1 preferentially acetylates amino-terminal peptide tails of histones H3 and H4.
Figure 4: SRC-1 and PCAF interact in vitro and in whole cells.

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Acknowledgements

We thank P. Samora and L. Gong for technical support of the experiments; D. P. Edwards for assistance with monoclonal antibody production; Y. Nakatani for the human Flag-PCAF plasmid; and A. Wolffe and J. Wong for discussion. This work was supported by an NIH NRSA postdoctoral fellowship (T.E.S.), a TALENT stipend from the Netherlands Organization for Scientific Research (G.J.) and an NIH grant (B.W.O.).

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Author notes

  1. Thomas E. Spencer, Guido Jenster, C. David Allis, Jianxin Zhou and Craig A. Mizzen: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cell Biology, One Baylor Plaza, Baylor College of Medicine, Houston, 77030, Texas, USA

    Thomas E. Spencer, Guido Jenster, Mark M. Burcin, Neil J. McKenna, Sergio A. Onate, Sophia Y. Tsai, Ming-Jer Tsai & Bert W. O'Malley

  2. Department of Biology, University of Rochester, Rochester, 14627, New York, USA

    C. David Allis, Jianxin Zhou & Craig A. Mizzen

  3. Department of Urology, M.D. Anderson Cancer Center, University of Texas, Houston, 77030, Texas, USA

    Guido Jenster

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Correspondence to Bert W. O'Malley.

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Spencer, T., Jenster, G., Burcin, M. et al. Steroid receptor coactivator-1 is a histone acetyltransferase. Nature 389, 194–198 (1997). https://doi.org/10.1038/38304

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