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Publication : Regulation of mouse steroidogenesis by WHISTLE and JMJD1C through histone methylation balance.

First Author  Kim SM Year  2010
Journal  Nucleic Acids Res Volume  38
Issue  19 Pages  6389-403
PubMed ID  20530532 Mgi Jnum  J:173421
Mgi Id  MGI:5014016 Doi  10.1093/nar/gkq491
Citation  Kim SM, et al. (2010) Regulation of mouse steroidogenesis by WHISTLE and JMJD1C through histone methylation balance. Nucleic Acids Res 38(19):6389-403
abstractText  The dynamic exchange of histone lysine methylation status by histone methyltransferases and demethylases has been previously implicated as an important factor in chromatin structure and transcriptional regulation. Using immunoaffinity TAP analysis, we purified the WHISTLE-interacting protein complexes, which include the heat shock protein HSP90alpha and the jumonji C-domain harboring the histone demethylase JMJD1C. In this study, we demonstrate that JMJD1C specifically demethylates histone H3K9 mono- and di-methylation, and mediates transcriptional activation. We also provide evidence suggesting that both WHISTLE and JMJD1C performs functions in the development of mouse testes by regulating the expression of the steroidogenesis marker, p450c17, via SF-1-mediated transcription. Furthermore, we demonstrate that WHISTLE is recruited to the p450c17 promoter via SF-1 and represses the transcription of prepubertal stages of steroidogenesis, after which JMJD1C replaces WHISTLE and activates the expression of target genes via SF-1-mediated interactions. Our results demonstrate that the histone methylation balance mediated by HMTase WHISTLE and demethylase JMJD1C perform a transcriptional regulatory function in mouse testis development.
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