Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA.
Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA.
Trends Genet. 2020 Jan;36(1):30-43. doi: 10.1016/j.tig.2019.10.004. Epub 2019 Nov 18.
Epigenetic mechanisms play essential roles in determining distinct cell fates during the development of multicellular organisms. Histone proteins represent crucial epigenetic components that help specify cell identities. Previous work has demonstrated that during the asymmetric cell division of Drosophila male germline stem cells (GSCs), histones H3 and H4 are asymmetrically inherited, such that pre-existing (old) histones are segregated towards the self-renewing GSC whereas newly synthesized (new) histones are enriched towards the differentiating daughter cell. In order to further understand the molecular mechanisms underlying this striking phenomenon, two key questions must be answered: when and how old and new histones are differentially incorporated by sister chromatids, and how epigenetically distinct sister chromatids are specifically recognized and segregated. Here, we discuss recent advances in our understanding of the molecular mechanisms and cellular bases underlying these fundamental and important biological processes responsible for generating two distinct cells through one cell division.
表观遗传机制在多细胞生物的发育过程中决定不同细胞命运方面发挥着重要作用。组蛋白是重要的表观遗传成分,有助于确定细胞的身份。先前的研究表明,在果蝇雄性生殖干细胞(GSCs)的不对称细胞分裂过程中,组蛋白 H3 和 H4 呈不对称遗传,即旧组蛋白被分配到自我更新的 GSC 中,而新合成的(新)组蛋白则富集到分化的子细胞中。为了进一步了解这一显著现象的分子机制,必须回答两个关键问题:姐妹染色单体何时以及如何差异地掺入新旧组蛋白,以及如何特异性识别和分离具有不同表观遗传的姐妹染色单体。在这里,我们讨论了我们对这些基本和重要的生物学过程的分子机制和细胞基础的理解的最新进展,这些过程通过一次细胞分裂产生两个不同的细胞。