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AuthorHu, Yu-Jie
AuthorBelaghzal, Houda
AuthorHsiao, Wen-Yu
AuthorQi, Jun
AuthorBradner, James E.
AuthorGuertin, David A.
AuthorSif, Said
AuthorImbalzano, Anthony N.
Available date2016-11-10T09:19:27Z
Publication Date2015-06-27
Publication NameNucleic Acids Researchen_US
Identifierhttp://dx.doi.org/10.1093/nar/gkv645
CitationHu Y-J, Belaghzal H, Hsiao W-Y, et al. Transcriptional and post-transcriptional control of adipocyte differentiation by Jumonji domain-containing protein 6. Nucleic Acids Research. 2015;43(16):7790-7804.
ISSN0305-1048
URIhttp://hdl.handle.net/10576/4988
AbstractJumonji domain-containing protein 6 (JMJD6) is a nuclear protein involved in histone modification, transcription and RNA processing. Although JMJD6 is crucial for tissue development, the link between its molecular functions and its roles in any given differentiation process is unknown. We report that JMJD6 is required for adipogenic gene expression and differentiation in a manner independent of Jumonji C domain catalytic activity. JMJD6 knockdown led to a reduction of C/EBPβ and C/EBPδ protein expression without affecting mRNA levels in the early phase of differentiation. However, ectopic expression of C/EBPβ and C/EBPδ did not rescue differentiation. Further analysis demonstrated that JMJD6 was associated with the Pparγ2 and Cebpα loci and putative enhancers. JMJD6 was previously found associated with bromodomain and extra-terminal domain (BET) proteins, which can be targeted by the bromodomain inhibitor JQ1. JQ1 treatment prevented chromatin binding of JMJD6, Pparγ2 and Cebpα expression, and adipogenic differentiation, yet had no effect on C/EBPβ and C/EBPδ expression or chromatin binding. These results indicate dual roles for JMJD6 in promoting adipogenic gene expression program by post-transcriptional regulation of C/EBPβ and C/EBPδ and direct transcriptional activation of Pparγ2 and Cebpα during adipocyte differentiation.
SponsorNational Institutes of Health (NIH) [DK084278 to S.S. and A.N.I., GM56244 to A.N.I., DK32520 to UMass Medical School Diabetes and Endocrine Research Center]. Funding for open access charge: NIH [GM56244].
Languageen
PublisherOxford University Press
SubjectGene regulation
SubjectChromatin and Epigenetics
TitleTranscriptional and post-transcriptional control of adipocyte differentiation by Jumonji domain-containing protein 6
TypeArticle
Pagination7790-7804
Issue Number16
Volume Number43
ESSN1362-4962


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