PBAF chromatin remodeler complexes that mediate meiotic transitions in mouse.
PBAF chromatin remodeler complexes that mediate meiotic transitions in mouse.
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DOI：
10.1242/dev.199967
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发表时间：
2022-09
期刊：
影响因子：
4.6
通讯作者：
R. O. de Castro;L. Previato de Almeida;Agustín Carbajal;Irma Gryniuk;R. Pezza
中科院分区：
文献类型：
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作者：
R. O. de Castro;L. Previato de Almeida;Agustín Carbajal;Irma Gryniuk;R. Pezza
哺乳动物的配子发生包括高度调控的发育转变。这些与转录的变化有关，转录的变化导致在配子发育的不同阶段观察到的基因表达的特征模式，其中包括具有关键减数分裂功能的特定活动。 SWI/SNF 染色质重塑因子被认为是基因转录和 DNA 修复的调节因子，但对其组成和减数分裂中的功能知之甚少。我们已经生成了 ARID2（PBAF 的特定调节亚基）配子特异性条件敲除小鼠，并将其表型与 BRG1 敲除（PBAF/BAF 复合物的催化亚基）进行了比较。虽然 Brg1Δ/Δ 敲除在减数分裂的早期阶段起作用并导致细胞在粗线期停滞，但 ARID2 活性显然是在前期 I 结束时需要的。在 Arid2Δ/Δ 敲除中观察到的纺锤体组装和染色体-纺锤体附着的显着缺陷归因于着丝粒处染色体分离的主要调节因子极光 B 激酶的增加。进一步的遗传和生化分析表明，形成了典型的 PBAF 和包含 ARID2 和 PBRM1 作为核心成分的独立于 BRG1 的复合物。这些数据支持一个模型，其中不同的 PBAF 复合物调节减数分裂和配子发生的不同阶段。
Gametogenesis in mammals encompasses highly regulated developmental transitions. These are associated with changes in transcription that cause characteristic patterns of gene expression observed during distinct stages of gamete development, which include specific activities with critical meiotic functions. SWI/SNF chromatin remodelers are recognized regulators of gene transcription and DNA repair, but their composition and functions in meiosis are poorly understood. We have generated gamete-specific conditional knockout mice for ARID2, a specific regulatory subunit of PBAF, and have compared its phenotype with BRG1 knockouts, the catalytic subunit of PBAF/BAF complexes. While Brg1Δ/Δ knockout acts at an early stage of meiosis and causes cell arrest at pachynema, ARID2 activity is apparently required at the end of prophase I. Striking defects in spindle assembly and chromosome-spindle attachment observed in Arid2Δ/Δ knockouts are attributed to an increase in aurora B kinase, a master regulator of chromosome segregation, at centromeres. Further genetic and biochemical analyses suggest the formation of a canonical PBAF and a BRG1-independent complex containing ARID2 and PBRM1 as core components. The data support a model in which different PBAF complexes regulate different stages of meiosis and gametogenesis.