A non-canonical BRD9-containing BAF chromatin remodeling complex regulates naive pluripotency in mouse embryonic stem cells.,Nature Communications

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A non-canonical BRD9-containing BAF chromatin remodeling complex regulates naive pluripotency in mouse embryonic stem cells.
Nature Communications ( IF 14.7 ) Pub Date : 2018-12-03 , DOI: 10.1038/s41467-018-07528-9
Jovylyn Gatchalian ₁ , Shivani Malik ₁ , Josephine Ho ₁ , Dong-Sung Lee ₂ , Timothy W R Kelso ₁ , Maxim N Shokhirev ₃ , Jesse R Dixon ₂ , Diana C Hargreaves ₁

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The role of individual subunits in the targeting and function of the mammalian BRG1-associated factors (BAF) complex in embryonic stem cell (ESC) pluripotency maintenance has not yet been elucidated. Here we find that the Bromodomain containing protein 9 (BRD9) and Glioma tumor suppressor candidate region gene 1 (GLTSCR1) or its paralog GLTSCR1-like (GLTSCR1L) define a smaller, non-canonical BAF complex (GBAF complex) in mouse ESCs that is distinct from the canonical ESC BAF complex (esBAF). GBAF and esBAF complexes are targeted to different genomic features, with GBAF co-localizing with key regulators of naive pluripotency, which is consistent with its specific function in maintaining naive pluripotency gene expression. BRD9 interacts with BRD4 in a bromodomain-dependent fashion, which leads to the recruitment of GBAF complexes to chromatin, explaining the functional similarity between these epigenetic regulators. Together, our results highlight the biological importance of BAF complex heterogeneity in maintaining the transcriptional network of pluripotency.

中文翻译：

含有非经典 BRD9 的 BAF 染色质重塑复合物可调节小鼠胚胎干细胞的幼稚多能性。

尚未阐明单个亚基在哺乳动物 BRG1 相关因子 (BAF) 复合物在胚胎干细胞 (ESC) 多能性维持中的靶向和功能中的作用。在这里，我们发现含有蛋白质 9 (BRD9) 和神经胶质瘤肿瘤抑制候选区域基因 1 (GLTSCR1) 或其旁系同源 GLTSCR1 样 (GLTSCR1L) 的 Bromodomain 在小鼠 ESC 中定义了一个更小的非规范 BAF 复合体（GBAF 复合体），即不同于规范的 ESC BAF 复合体 (esBAF)。GBAF 和 esBAF 复合物针对不同的基因组特征，GBAF 与幼稚多能性的关键调节因子共定位，这与其维持幼稚多能性基因表达的特定功能一致。BRD9 以溴结构域依赖性方式与 BRD4 相互作用，导致 GBAF 复合物募集到染色质，解释这些表观遗传调节剂之间的功能相似性。总之，我们的结果强调了 BAF 复杂异质性在维持多能性转录网络中的生物学重要性。

更新日期：2018-12-03

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