Elsevier

Stem Cell Research

Volume 24, October 2017, Pages 195-202
Stem Cell Research

DMRT proteins and coordination of mammalian spermatogenesis

https://doi.org/10.1016/j.scr.2017.07.026Get rights and content
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Highlights

  • DMRT proteins are conserved transcriptional regulators of sexual differentiation.

  • DMRT1 regulates several stages of pre-meiotic male germ cell development.

  • DMRT6 helps coordinate the transition of male germ cells from mitosis to meiosis.

  • DMRT7 is required in spermatocytes for formation of post-meiotic sex chromatin.

  • Unusual DNA binding may help explain the regulatory versatility of DMRT proteins.

Abstract

DMRT genes encode a deeply conserved family of transcription factors that share a unique DNA binding motif, the DM domain. DMRTs regulate development in a broad variety of metazoans and they appear to have controlled sexual differentiation for hundreds of millions of years. In mice, starting during embryonic development, three Dmrt genes act sequentially to help establish and maintain spermatogenesis. Dmrt1 has notably diverse functions that include repressing pluripotency genes and promoting mitotic arrest in embryonic germ cells, reactivating prospermatogonia perinatally, establishing and maintaining spermatogonial stem cells (SSCs), promoting spermatogonial differentiation, and controlling the mitosis/meiosis switch. Dmrt6 acts in differentiating spermatogonia to coordinate an orderly exit from the mitotic/spermatogonial program and allow proper timing of entry to the meiotic/spermatocyte program. Finally, Dmrt7 takes over during the first meiotic prophase to help choreograph a transition in histone modifications that maintains transcriptional silencing of the sex chromosomes. The combined action of these three Dmrt genes helps ensure robust and sustainable spermatogenesis.

Keywords

DMRT
Spermatogenesis
SSC
Testis

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