Identification and characterization of BEND2 as a key regulator of meiosis during mouse spermatogenesis.
Identification and characterization of BEND2 as a key regulator of meiosis during mouse spermatogenesis.
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DOI：
10.1126/sciadv.abn1606
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发表时间：
2022-05-27
期刊：
影响因子：
13.6
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中科院分区：
文献类型：
--
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染色质状态在精子发生过程中经历整体变化，对于减数分裂的启动和进展至关重要。然而，所涉及的关键调节因子和潜在的分子机制仍有待揭示。在此，我们报告小鼠 BEND2 在减数分裂起始前后的生精细胞中特异性表达，并且在减数分裂进展中发挥重要作用。雄性小鼠中的 Bend2 基因敲除会阻止从接合体到粗线体的减数分裂，破坏突触和 DNA 双链断裂修复，并诱导非同源染色体配对。 BEND2 与染色质相关蛋白相互作用，这些蛋白是某些转录抑制复合物的组成部分。在不同染色质状态下鉴定出 BEND2 结合位点，并在简单序列重复中富集。 BEND2 抑制参与减数分裂起始、调节染色质可及性和 H3K4me3 修饰的基因表达。因此，我们的研究确定 BEND2 是小鼠精子发生过程中减数分裂、基因表达和染色质状态的一个先前未知的关键调节因子。 BEND2 对于减数分裂至关重要，因为它与染色质调节剂相互作用并调节基因表达。
The chromatin state, which undergoes global changes during spermatogenesis, is critical to meiotic initiation and progression. However, the key regulators involved and the underlying molecular mechanisms remain to be uncovered. Here, we report that mouse BEND2 is specifically expressed in spermatogenic cells around meiotic initiation and that it plays an essential role in meiotic progression. Bend2 gene knockout in male mice arrested meiosis at the transition from zygonema to pachynema, disrupted synapsis and DNA double-strand break repair, and induced nonhomologous chromosomal pairing. BEND2 interacted with chromatin-associated proteins that are components of certain transcription-repressor complexes. BEND2-binding sites were identified in diverse chromatin states and enriched in simple sequence repeats. BEND2 inhibited the expression of genes involved in meiotic initiation and regulated chromatin accessibility and the modification of H3K4me3. Therefore, our study identified BEND2 as a previously unknown key regulator of meiosis, gene expression, and chromatin state during mouse spermatogenesis. BEND2 is essential for meiosis because it interacts with chromatin modulators and regulates gene expression.
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