Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, 48149 Münster, Germany.
Institute of Medical Informatics, University of Münster, 48149 Münster, Germany.
Cells. 2022 Apr 15;11(8):1354. doi: 10.3390/cells11081354.
The murine esBAF complex plays a major role in the regulation of gene expression during stem cell development and differentiation. As one of its core subunits, Smarcb1 is indispensable for its function and its loss is connected to neurodevelopmental disorders and participates in the carcinogenesis of entities such as rhabdoid tumours. We explored how Smarcb1 regulates gene programs in murine embryonic stem cells (mESC) and in this way orchestrates differentiation. Our data underline the importance of Smarcb1 expression and function for the development of the nervous system along with basic cellular functions, such as cell adhesion and cell organisation. Using ChIP-seq, we were able to portray the consequences of Smarcb1 knockdown (kd) for the binding of esBAF and PRC2 as well as its influence on histone marks H3K27me3, H3K4me3 and H3K27ac. Their signals are changed in gene and enhancer regions of genes connected to nervous system development and offers a plausible explanation for changes in gene expression. Further, we describe a group of genes that are, despite increased BAF binding, suppressed after Smarcb1 kd by mechanisms independent of PRC2 function.
小鼠 esBAF 复合物在干细胞发育和分化过程中的基因表达调控中起着重要作用。作为其核心亚基之一，Smarcb1 对于其功能是不可或缺的，其缺失与神经发育障碍有关，并参与横纹肌瘤等实体瘤的癌变。我们探讨了 Smarcb1 如何在小鼠胚胎干细胞 (mESC) 中调节基因程序，并以此来协调分化。我们的数据强调了 Smarcb1 表达和功能对于神经系统发育以及细胞粘附和细胞组织等基本细胞功能的重要性。通过 ChIP-seq，我们能够描绘 Smarcb1 敲低 (kd) 对 esBAF 和 PRC2 结合的影响，以及对组蛋白标记 H3K27me3、H3K4me3 和 H3K27ac 的影响。它们的信号在与神经系统发育相关的基因和增强子区域的基因中发生改变，为基因表达的变化提供了一个合理的解释。此外，我们描述了一组基因，尽管 BAF 结合增加，但在 Smarcb1 kd 后，通过独立于 PRC2 功能的机制被抑制。
