This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 21/4/843    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Aoyagi, S. Articles by Archer, T. K. Search for Related Content PubMed PubMed Citation Articles by Aoyagi, S. Articles by Archer, T. K.

Dynamic Histone Acetylation/Deacetylation with Progesterone Receptor-Mediated Transcription

Chromatin and Gene Expression Section, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709

Address requests for reprints and all correspondence to: Dr. Trevor K. Archer, Chromatin and Gene Expression Section, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, 111 Alexander Drive, P.O. Box 12233 (MD D4-01), Research Triangle Park, North Carolina 27709. E-mail: archer1{at}niehs.nih.gov.

Histone acetylation is a highly dynamic posttranslational modification that plays an important role in gene expression. Previous work showed that promoter histone deacetylation is accompanied by progesterone receptor (PR)-mediated activation of the mouse mammary tumor virus (MMTV) promoter. We investigated the role of this deacetylation and found that this histone deacetylation is not a singular event. In fact, histone acetylation at the MMTV promoter is highly dynamic, with an initial increase in acetylation followed by an eventual net deacetylation of histone H4. The timing of increase in acetylation of H4 coincides with the time at which PR, RNA polymerase II, and histone acetyltransferases cAMP response element-binding protein (CREB)-binding protein and p300 are recruited to the MMTV promoter. The timing in which histone H4 deacetylation occurs (after PR and RNA polymerase II recruitment) and the limited effect that trichostatin A and small interfering RNA knockdown of histone deacetylase (HDAC)3 have on MMTV transcription suggests that this deacetylation activity is not required for the initiation of PR-mediated transcription. Interestingly, two HDACs, HDAC1 and HDAC3, are already present at the MMTV before transcription activation. HDAC association at the MMTV promoter fluctuates during the hormone treatment. In particular, HDAC3 is temporarily undetected at the MMTV promoter within minutes after hormone treatment when the histone H4 acetylation increases but returns to the promoter near the time when histone acetylation levels start to decline. These results demonstrate the dynamic nature of coactivator/corepressor-promoter association and histone modifications such as acetylation during a transcription activation event.

NURSA Molecule Pages Link:

Nuclear Receptors:   PR

Coregulators:   CBP  |  p300  |  HDAC1  |  HDAC3

Ligands:   Mifepristone  |  R5020

This article has been cited by other articles:

				M. Malinen, A. Saramaki, A. Ropponen, T. Degenhardt, S. Vaisanen, and C. Carlberg Distinct HDACs regulate the transcriptional response of human cyclin-dependent kinase inhibitor genes to trichostatin A and 1{alpha},25-dihydroxyvitamin D3 Nucleic Acids Res., January 17, 2008; 36(1): 121 - 132. [Abstract] [Full Text] [PDF]

				S. Aoyagi and T. K. Archer Nicotinamide Uncouples Hormone-Dependent Chromatin Remodeling from Transcription Complex Assembly Mol. Cell. Biol., January 1, 2008; 28(1): 30 - 39. [Abstract] [Full Text] [PDF]

				H. K. Kinyamu and T. K. Archer Proteasome Activity Modulates Chromatin Modifications and RNA Polymerase II Phosphorylation To Enhance Glucocorticoid Receptor-Mediated Transcription Mol. Cell. Biol., July 1, 2007; 27(13): 4891 - 4904. [Abstract] [Full Text] [PDF]