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Cell-Type-Specific Control of Enhancer Activity by H3K9 Trimethylation.
MedLine Citation:
PMID:  22633489     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Cell-type-specific control of gene expression is critical for the development of multicellular organisms. To investigate the mechanisms which underlie this, we have studied the regulation of the model genes Mdc and Il12b, whose stimulus-induced expression is tightly restricted to specific cells of the immune system. Surprisingly, we find that neither the promoter nor the enhancer sequences of these genes are sufficient to direct this cell-type specificity. Instead, the activities of upstream enhancers are repressed in nonexpressing cells by high levels of trimethylated H3K9 in their flanking regions. Genome-wide analysis indicates that this manner of regulation is shared by numerous enhancers of cell-type-specific genes. In dendritic cells and macrophages, the stimulus-induced demethylase Jmjd2d controls H3K9me3 levels at these regions, and is thereby required for Mdc and Il12b transcription. By experimentally assaying multiple enhancers in a variety of cell types, we show that regulation by H3K9me3 is a widely used mechanism which imparts specificity to the activities of otherwise broadly functional enhancers.
Authors:
Yina Zhu; Dominic van Essen; Simona Saccani
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular cell     Volume:  46     ISSN:  1097-4164     ISO Abbreviation:  Mol. Cell     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9802571     Medline TA:  Mol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  408-23     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Department of Cellular and Molecular Immunology, Max Planck Institute for Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany.
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