This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Stossi, F.
Right arrow Articles by Katzenellenbogen, B. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stossi, F.
Right arrow Articles by Katzenellenbogen, B. S.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 2009, p. 1749-1759, Vol. 29, No. 7
0270-7306/09/$08.00+0     doi:10.1128/MCB.01476-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Estrogen Receptor Alpha Represses Transcription of Early Target Genes via p300 and CtBP1{triangledown}

Fabio Stossi,1 Zeynep Madak-Erdogan,2 and Benita S. Katzenellenbogen1,2*

Department of Molecular and Integrative Physiology,1 Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 618012

Received 19 September 2008/ Returned for modification 29 October 2008/ Accepted 20 January 2009

The regulation of gene expression by nuclear receptors controls the phenotypic properties and diverse biologies of target cells. In breast cancer cells, estrogen receptor alpha (ER{alpha}) is a master regulator of transcriptional stimulation and repression, yet the mechanisms by which agonist-bound ER{alpha} elicits repression are poorly understood. We analyzed early estrogen-repressed genes and found that ER{alpha} is recruited to ER{alpha} binding sites of these genes, albeit more transiently and less efficiently than for estrogen-stimulated genes. Of multiple cofactors studied, only p300 was recruited to ER{alpha} binding sites of repressed genes, and its knockdown prevented estrogen-mediated gene repression. Because p300 is involved in transcription initiation, we tested whether ER{alpha} might be trying to stimulate transcription at repressed genes, with ultimately failure and a shift to a repressive program. We found that estrogen increases transcription in a rapid but transient manner at early estrogen-repressed genes but that this is followed by recruitment of the corepressor CtBP1, a p300-interacting partner that plays an essential role in the repressive process. Thus, at early estrogen-repressed genes, ER{alpha} initiates transient stimulation of transcription but fails to maintain the transcriptional process observed at estrogen-stimulated genes; rather, it uses p300 to recruit CtBP1-containing complexes, eliciting chromatin modifications that lead to transcriptional repression.

* Corresponding author. Mailing address: University of Illinois, Department of Molecular and Integrative Physiology, 524 Burrill Hall, 407 South Goodwin Avenue, Urbana, IL 61801-3704. Phone: (217) 333-9769. Fax: (217) 244-9906. E-mail: katzenel{at}illinois.edu

{triangledown} Published ahead of print on 2 February 2009.

Molecular and Cellular Biology, April 2009, p. 1749-1759, Vol. 29, No. 7
0270-7306/09/$08.00+0     doi:10.1128/MCB.01476-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Palijan, A., Fernandes, I., Verway, M., Kourelis, M., Bastien, Y., Tavera-Mendoza, L. E., Sacheli, A., Bourdeau, V., Mader, S., White, J. H. (2009). Ligand-dependent Corepressor LCoR Is an Attenuator of Progesterone-regulated Gene Expression. J. Biol. Chem. 284: 30275-30287 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»