Journal article
Epigenetic regulation of mouse sex determination by the histone demethylase Jmjd1a
S Kuroki, S Matoba, M Akiyoshi, Y Matsumura, H Miyachi, N Mise, K Abe, A Ogura, D Wilhelm, P Koopman, M Nozaki, Y Kanai, Y Shinkai, M Tachibana
Science | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2013
Abstract
Developmental gene expression is defined through cross-talk between the function of transcription factors and epigenetic status, including histone modification. Although several transcription factors play crucial roles in mammalian sex determination, how epigenetic regulation contributes to this process remains unknown. We observed male-to-female sex reversal in mice lacking the H3K9 demethylase Jmjd1a and found that Jmjd1a regulates expression of the mammalian Y chromosome sex-determining gene Sry. Jmjd1a directly and positively controls Sry expression by regulating H3K9me2 marks. These studies reveal a pivotal role of histone demethylation in mammalian sex determination.
Grants
Awarded by Japan Society for the Promotion of Science
Funding Acknowledgements
We are especially grateful to T. Nakano for critical advice during the manuscript preparation. We thank K. Morohashi for antibodies to Nr5a1; H. Kimura for antibodies to histone; and T. Hara for fluorescence-activated cell sorting analysis support. We are also grateful to T. Matsui, G. Nagamatsu, and the members of the Tachibana laboratory for technical support. This work was supported by grants from the Funding Program for Next Generation World-Leading Researchers (M.T.). The microarray data have been deposited in the Gene Expression Omnibus and given the accession number GSE49513.