HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0094v1 200/3/311    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Muller, P. Articles by Strom, A. Search for Related Content PubMed PubMed Citation Articles by Muller, P. Articles by Strom, A.

P Muller, Dept of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
K Merrell, Dept of Microbiology and Molecular Biology, Brigham Young University, Provo, United States
J Crofts, Dept of Microbiology and Molecular Biology, Brigham Young University, Provo, United States
C Ronnlund, Dept of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
C Lin, Dept of Microbiology and Molecular Biology, Brigham Young University, Provo, United States
J Gustafsson, Dept of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
A Strom, Dept of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden

Correspondence: Patrick Muller, Email: patrick.muller{at}ki.se

Abstract

Regulation of Hairy and Enhancer of Split homologue-1 (HES-1) by estradiol and all-trans retinoic acid affects proliferation of human breast cancer cells. Here we identify and characterize cis-regulatory elements involved in HES-1 regulation. In the distal 5' promoter of the HES-1 gene, we found a retinoic acid response element and in the distal 3' region, an estrogen receptor (ER) binding site. The ER binding site, composed of an estrogen response element (ERE) and an ERE half-site, is important both for ER binding and transcriptional regulation. ChIP assays revealed that ER is recruited to the ERE and associates with the HES-1 promoter. We also show recruitment of nuclear receptor co-regulators to the ERE in response to estradiol, followed by a decrease in histone acetylation and RNA polymerase II docking in the HES-1 promoter region. Our findings are consistent with a novel type of repressive estrogen responsive element in the distal 3' region of the HES-1 gene.