Zhang Teng, Zarkower David
Department of Genetics, Cell Biology, and Development, and Developmental Biology Center, University of Minnesota Medical School, 6-160 Jackson Hall, 321 Church St. SE, Minneapolis, MN 55455, USA.
Department of Genetics, Cell Biology, and Development, and Developmental Biology Center, University of Minnesota Medical School, 6-160 Jackson Hall, 321 Church St. SE, Minneapolis, MN 55455, USA; University of Minnesota Masonic Cancer Center, Minneapolis, MN 55455, USA.
Stem Cell Res. 2017 Oct;24:195-202. doi: 10.1016/j.scr.2017.07.026. Epub 2017 Jul 25.
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.
DMRT基因编码一类高度保守的转录因子家族，它们共享一个独特的DNA结合基序，即DM结构域。DMRTs在多种后生动物中调节发育，并且似乎已经控制性别分化达数亿年之久。在小鼠中，从胚胎发育开始，三个Dmrt基因依次发挥作用，以帮助建立和维持精子发生。Dmrt1具有特别多样的功能，包括抑制多能性基因和促进胚胎生殖细胞的有丝分裂停滞，在围产期重新激活精原细胞，建立和维持精原干细胞（SSCs），促进精原细胞分化，以及控制有丝分裂/减数分裂转换。Dmrt6在分化中的精原细胞中起作用，以协调从有丝分裂/精原细胞程序的有序退出，并允许适时进入减数分裂/精母细胞程序。最后，Dmrt7在第一次减数分裂前期发挥作用，以帮助编排组蛋白修饰的转变，从而维持性染色体的转录沉默。这三个Dmrt基因的共同作用有助于确保强大而可持续的精子发生。
