This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager NURSA Molecule Pages Link Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Leong, H. Articles by Greene, G. L. Search for Related Content PubMed PubMed Citation Articles by Leong, H. Articles by Greene, G. L.

Recruitment of Histone Deacetylase 4 to the N-Terminal Region of Estrogen Receptor

The Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois 60637

Address all correspondence and requests for reprints to: Geoffrey L. Greene, The Ben May Institute for Cancer Research, The University of Chicago, Center for Integrative Sciences, Room W330, 929 East 57th Street, Chicago, Illinois 60637. E-mail: ggreene{at}uchicago.edu.

Transcriptional activation of estrogen receptor (ER) is regulated by the ligand-dependent activation function 2 and the constitutively active N-terminal activation function 1. To identify ER N-terminal-specific coregulators, we screened a breast cDNA library by T7 phage display and isolated histone deacetylase 4 (HDAC4). HDAC4 interacts with the ER N terminus both in vitro and in vivo. Presence of the ER DNA binding domain and hinge region reduce HDAC4 recruitment whereas full-length ER enhances recruitment. HDAC4 interaction is selective for the ER and not ERß N terminus and occurs in the nucleus. We demonstrate in vivo that HDAC4 is recruited by the N terminus to the promoter of an endogenous estrogen responsive gene. HDAC4 suppresses transcriptional activation of ER by estrogen and selective ER modulators (SERMs) such as tamoxifen in a cell type-dependent manner. Consistently, silencing of HDAC4 promotes the agonist effect of SERMs (tamoxifen and raloxifene) in a cell type-specific manner. These findings indicate a role for HDAC4 in regulating ER activity as a novel N-terminal coregulator and uncover a mechanism by which certain cell types regulate SERM behavior.

NURSA Molecule Pages Link:

Nuclear Receptors:   ERα  |  ERβ

Coregulators:   LCoR  |  HDAC4  |  REA  |  HDAC1  |  HDAC2  |  HDAC3  |  MTA1  |  NCOR  |  SMRT

Ligands:   17β-Estradiol  |  Diethylstilbestrol  |  Raloxifene

This article has been cited by other articles:

				S. Malik, S. Jiang, J. P. Garee, E. Verdin, A. V. Lee, B. W. O'Malley, M. Zhang, N. S. Belaguli, and S. Oesterreich Histone Deacetylase 7 and FoxA1 in Estrogen-Mediated Repression of RPRM Mol. Cell. Biol., January 15, 2010; 30(2): 399 - 412. [Abstract] [Full Text] [PDF]

				E. van Rooij, J. Fielitz, L. B. Sutherland, V. L. Thijssen, H. J. Crijns, M. J. Dimaio, J. Shelton, L. J. De Windt, J. A. Hill, and E. N. Olson Myocyte Enhancer Factor 2 and Class II Histone Deacetylases Control a Gender-Specific Pathway of Cardioprotection Mediated by the Estrogen Receptor Circ. Res., January 8, 2010; 106(1): 155 - 165. [Abstract] [Full Text] [PDF]

				K. Nagayama, S. Sasaki, A. Matsushita, K. Ohba, H. Iwaki, H. Matsunaga, S. Suzuki, H. Misawa, K. Ishizuka, Y. Oki, et al. Inhibition of GATA2-dependent transactivation of the TSH{beta} gene by ligand-bound estrogen receptor {alpha} J. Endocrinol., October 1, 2008; 199(1): 113 - 125. [Abstract] [Full Text] [PDF]

				A. Sayeed, S. D. Konduri, W. Liu, S. Bansal, F. Li, and G. M. Das Estrogen Receptor {alpha} Inhibits p53-Mediated Transcriptional Repression: Implications for the Regulation of Apoptosis Cancer Res., August 15, 2007; 67(16): 7746 - 7755. [Abstract] [Full Text] [PDF]

				M. Y. Kim, E. M. Woo, Y. T. E. Chong, D. R. Homenko, and W. L. Kraus Acetylation of Estrogen Receptor {alpha} by p300 at Lysines 266 and 268 Enhances the Deoxyribonucleic Acid Binding and Transactivation Activities of the Receptor Mol. Endocrinol., July 1, 2006; 20(7): 1479 - 1493. [Abstract] [Full Text] [PDF]