title: Jmjd3 and UTX play a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression.
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.
authors.affiliation: University of Washington, Seattle, WA 98195, USA.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Miller
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Mohn
authors.forename: Amy S
authors.initials: AS
authors.lastname: Weinmann
mesh_terms: D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism; D056466:Histone Demethylases; D006657:Histones / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D020825:T-Box Domain Proteins / Q000172:deficiency / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D009687:Nuclear Proteins; C445179:SWI-SNF-B chromatin-remodeling complex; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D007371:Interferon-gamma; D056466:Histone Demethylases; D056484:Jumonji Domain-Containing Histone Demethylases; C111778:Utx protein, mouse; C523761:Kdm6b protein, mouse; C513194:Smarca4 protein, mouse; D004265:DNA Helicases; D008239:Lysine