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FEBS Lett. 2011 May 6;585(9):1269-75. doi: 10.1016/j.febslet.2011.03.059. Epub 2011 Apr 1.

Nuclear receptor SHP inhibition of Dnmt1 expression via ERRγ.

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  • 1Departments of Medicine and Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84132, United States.

Abstract

We describe a transcriptional mechanism regulating the expression of Dnmt1 by nuclear receptors. We show that ERRγ functions as a transcriptional activator of mouse and human Dnmt1 expression by direct binding to its response elements (ERE1/ERE2) in the dnmt1/DNMT1 promoters. The induction of Dnmt1 by ERRγ is repressed by SHP through SHP inhibition of ERRγ transactivity, diminishing ERRγ recruitment to the Dnmt1 promoter, and altering the conformation of local chromatin from an active mode by ERRγ to an inactive mode. Our study provides the first evidence for nuclear receptor mediated regulation of Dnmt1 expression through ERRγ and SHP crosstalk.

Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

PMID:
21459093
[PubMed - indexed for MEDLINE]
PMCID:
PMC3134389
Free PMC Article
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