Regulation of mouse steroidogenesis by WHISTLE and JMJD1C through histone methylation balance.
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 HSP90α 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.
Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, Korea.
Sung-Mi
SM
Kim
Ji-Young
JY
Kim
Nak-Won
NW
Choe
Ick-Hyun
IH
Cho
Ju-Ryoung
JR
Kim
Dong-Wook
DW
Kim
Jin-Ee
JE
Seol
Song Eun
SE
Lee
Hoon
H
Kook
Kwang-Il
KI
Nam
Hyun
H
Kook
Young-Yil
YY
Bhak
Sang-Beom
SB
Seo
D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D011495:Histone-Lysine N-Methyltransferase / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology; D006657:Histones / Q000378:metabolism; D056484:Jumonji Domain-Containing Histone Demethylases / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008745:Methylation; D051379:Mice; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D013256:Steroids / Q000096:biosynthesis*; D013737:Testis / Q000254:growth & development / Q000378:metabolism
D006657:Histones; D013256:Steroids; C554520:JMJD1c protein, mouse; D056484:Jumonji Domain-Containing Histone Demethylases; D013254:Steroid 17-alpha-Hydroxylase; D011495:Histone-Lysine N-Methyltransferase