NRF1 coordinates with DNA methylation to regulate spermatogenesis

Spermatogenesis is a highly coordinated process that requires tightly regulated gene expression programmed by transcription factors and epigenetic modifiers. In this study, we found that nuclear respiratory factor (NRF)‐1, a key transcription factor for mitochondrial biogenesis, cooperated with DNA methylation to directly regulate the expression of multiple germ cell–specific genes, including Asz1 . In addition, conditional ablation of NRF1 in gonocytes dramatically down‐regulated these germline genes, blocked germ cell proliferation, and subsequently led to male infertility in mice. Our data highlight a precise crosstalk between transcriptional regulation by NRF1 and epigenetic modulation during germ cell development and unequivocally demonstrate a novel role of NRF1 in spermatogenesis.—Wang, J., Tang, C., Wang, Q., Su, J., Ni, T., Yang, W., Wang, Y., Chen, W., Liu, X., Wang, S., Zhang, J., Song, H., Zhu, J., Wang, Y. NRF1 coordinates with DNA methylation to regulate spermatogenesis. FASEB J. 31, 4959–4970 (2017). www.fasebj.org