HDAC1 Acetylation Is Linked to Progressive Modulation of Steroid Receptor-Induced Gene Transcription

Yi Qiu, Yingming Zhao, Matthias Becker, Sam John, Bhavin S. Parekh, Suming Huang, Anindya Hendarwanto, Elisabeth D. Martinez, Yue Chen, Hanxin Lu, Nicholas L. Adkins, Diana A. Stavreva, Malgorzata Wiench, Philippe T. Georgel, R. Louis Schiltz, Gordon L. Hager

Research output: Contribution to journalArticlepeer-review

133 Scopus citations

Abstract

Although histone deacetylases (HDACs) are generally viewed as corepressors, we show that HDAC1 serves as a coactivator for the glucocorticoid receptor (GR). Furthermore, a subfraction of cellular HDAC1 is acetylated after association with the GR, and this acetylation event correlates with a decrease in promoter activity. HDAC1 in repressed chromatin is highly acetylated, while the deacetylase found on transcriptionally active chromatin manifests a low level of acetylation. Acetylation of purified HDAC1 inactivates its deacetylase activity, and mutation of the critical acetylation sites abrogates HDAC1 function in vivo. We propose that hormone activation of the receptor leads to progressive acetylation of HDAC1 in vivo, which in turn inhibits the deacetylase activity of the enzyme and prevents a deacetylation event that is required for promoter activation. These findings indicate that HDAC1 is required for the induction of some genes by the GR, and this activator function is dynamically modulated by acetylation.

Original languageEnglish (US)
Pages (from-to)669-679
Number of pages11
JournalMolecular Cell
Volume22
Issue number5
DOIs
StatePublished - Jun 9 2006
Externally publishedYes

Bibliographical note

Funding Information:
FLAG-tagged HDAC1 expression vector was obtained from Bruce Howard, NICHD, NIH. The mCherry FP construct was a generous gift from Roger Tsien, University of California, San Diego. FLAG-tagged HDAC1 baculovirus was kindly provided by Stuart Schreiber, Harvard University. GST-HDAC1 was a gift from Edward Seto, University of South Florida, and the RNA Pol II and p300 antibodies were provided by Kevin Gardner, NCI, Bethesda, Maryland. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. Y.Z. is supported by NIH grant CA 107943.

Keywords

  • DNA

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