Switching defective/sucrose non‐fermenting chromatin remodeling complex coordinates meiotic gene activation via promoter remodeling and Meiosin activation in female germline
Switching defective/sucrose non‐fermenting chromatin remodeling complex coordinates meiotic gene activation via promoter remodeling and Meiosin activation in female germline
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DOI：
10.1111/gtc.12990
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发表时间：
2022-11
期刊：
影响因子：
2.1
通讯作者：
Toshiaki Ito;M. Ohta;Atsuki Osada;A. Nishiyama;K. Ishiguro;T. Tamura;Y. Sekita;Tohru Kimura
中科院分区：
文献类型：
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作者：
Toshiaki Ito;M. Ohta;Atsuki Osada;A. Nishiyama;K. Ishiguro;T. Tamura;Y. Sekita;Tohru Kimura
哺乳动物的原始生殖细胞（PGCs）在胚胎卵巢中进入减数分裂并分化为原代卵母细胞。在此之前，我们证明了在缺乏Smarcb1 （Snf5）基因的条件敲除（CKO）小鼠的雌性生殖系细胞中，减数分裂基因诱导和减数分裂起始受到损害，Smarcb1 （Snf5）基因编码开关缺陷/蔗糖不发酵（SWI/SNF）复合体的核心亚基。在这项研究中，我们根据启动子可及性将Snf5 CKO雌性中表达较低水平的减数分裂基因分为两组。这些基因中74%的启动子在突变小鼠中显示出较低的可及性，而其余基因的启动子在没有SWI/SNF复合物的情况下被打开。值得注意的是，前一种基因包括减数分裂蛋白，它编码减数分裂基因激活所必需的转录调节因子。前者和后者基因的启动子主要分别被H3K27me3/二价和H3K4me3组蛋白标记修饰。前者基因的一个子集在缺乏多梳抑制复合物（PRCs）的女性PGCs中被提前激活。我们的研究结果指出了SWI/SNF复合物通过重塑PRC -抑制基因（包括减数球蛋白）来协调减数分裂基因激活的机制。
In mammals, primordial germ cells (PGCs) enter meiosis and differentiate into primary oocytes in embryonic ovaries. Previously, we demonstrated that meiotic gene induction and meiotic initiation were impaired in female germline cells of conditional knockout (CKO) mice lacking the Smarcb1 (Snf5) gene, which encodes a core subunit of the switching defective/sucrose non‐fermenting (SWI/SNF) complex. In this study, we classified meiotic genes expressed at lower levels in Snf5 CKO females into two groups based on promoter accessibility. The promoters of 74% of these genes showed lower accessibility in mutant mice, whereas those of the remaining genes were opened without the SWI/SNF complex. Notably, the former genes included Meiosin, which encodes a transcriptional regulator essential for meiotic gene activation. The promoters of the former and the latter genes were mainly modified with H3K27me3/bivalent and H3K4me3 histone marks, respectively. A subset of the former genes was precociously activated in female PGCs deficient in polycomb repressive complexes (PRCs). Our results point to a mechanism through which the SWI/SNF complex coordinates meiotic gene activation via the remodeling of PRC‐repressed genes, including Meiosin, in female germline cells.