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PMID: 21095589 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Jmjd3 and UTX play a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression.

Molecular cell ·Vol. 40 ·No. 4 ·2010-11-24 ·Pages 594-605

Miller SA, Mohn SE, Weinmann AS

Abstract

The stable and heritable H3K27-methyl mark suppresses transcription of lineage-specific genes in progenitor cells. During developmental transitions, histone demethylases are required to dramatically alter epigenetic and gene expression states to create new cell-specific profiles. It is unclear why demethylase proteins that antagonize polycomb-mediated repression continue to be expressed in terminally differentiated cells where further changes in H3K27 methylation could be deleterious. In this study, we show that the H3K27 demethylases, Jmjd3 and UTX, mediate a functional interaction between the lineage-defining T-box transcription factor family and a Brg1-containing SWI/SNF remodeling complex. Importantly, Jmjd3 is required for the coprecipitation of Brg1 with the T-box factor, T-bet, and this interaction is necessary for Ifng remodeling in differentiated Th1 cells. Thus, Jmjd3 has a required role in general chromatin remodeling that is independent from its H3K27 demethylase potential. This function for H3K27 demethylase proteins may explain their presence in differentiated cells where the epigenetic profile is already established.

MeSH Terms
Animals Cell Line Chromatin/metabolism Chromatin Assembly and Disassembly/genetics Chromosomal Proteins, Non-Histone/metabolism DNA Helicases/metabolism Histone Demethylases Histones/metabolism Interferon-gamma/genetics Jumonji Domain-Containing Histone Demethylases/metabolism Lysine/metabolism Mice Nuclear Proteins/metabolism Promoter Regions, Genetic/genetics Protein Binding Sequence Homology, Amino Acid T-Box Domain Proteins/deficiency,metabolism Transcription Factors/metabolism
Chemicals
Chromatin Chromosomal Proteins, Non-Histone Histones Nuclear Proteins SWI-SNF-B chromatin-remodeling complex T-Box Domain Proteins T-box transcription factor TBX21 Transcription Factors Interferon-gamma Histone Demethylases Jumonji Domain-Containing Histone Demethylases Utx protein, mouse Kdm6b protein, mouse Smarca4 protein, mouse DNA Helicases Lysine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Miller Sara A
University of Washington, Seattle, WA 98195, USA.
Mohn Sarah E
Weinmann Amy S
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-4164
DOI
10.1016/j.molcel.2010.10.028
Published
2010-11-24
Pages
594-605
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC3032266
Subset
IM
Grants
NIAID NIH HHS · AI07272 · United States
NIAID NIH HHS · R01 AI071272 · United States
NIGMS NIH HHS · 2T32 GM007270 · United States
NIGMS NIH HHS · T32 GM066698 · United States
NIGMS NIH HHS · T32 GM007270 · United States
NIAID NIH HHS · R01 AI061061-07 · United States
NIAID NIH HHS · T32 AI007272 · United States
NIAID NIH HHS · R01 AI061061 · United States
NIAID NIH HHS · R01 AI071272-10 · United States
NIAID NIH HHS · R56 AI061061 · United States
NIAID NIH HHS · AI061061 · United States
External Links
PubMed source DOI: 10.1016/j.molcel.2010.10.028 PMC Full Text View journal details
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