Nature ( IF 64.8 ) Pub Date : 2023-05-24 , DOI: 10.1038/s41586-023-06085-6 Zhexin Zhu 1 , Xiaolong Chen 2 , Ao Guo 3 , Trishabelle Manzano 1 , Patrick J Walsh 1 , Kendall M Wills 1 , Rebecca Halliburton 1 , Sandi Radko-Juettner 1, 4 , Raymond D Carter 1 , Janet F Partridge 1 , Douglas R Green 3 , Jinghui Zhang 2 , Charles W M Roberts 1
For cells to initiate and sustain a differentiated state, it is necessary that a ‘memory’ of this state is transmitted through mitosis to the daughter cells1,2,3. Mammalian switch/sucrose non-fermentable (SWI/SNF) complexes (also known as Brg1/Brg-associated factors, or BAF) control cell identity by modulating chromatin architecture to regulate gene expression4,5,6,7, but whether they participate in cell fate memory is unclear. Here we provide evidence that subunits of SWI/SNF act as mitotic bookmarks to safeguard cell identity during cell division. The SWI/SNF core subunits SMARCE1 and SMARCB1 are displaced from enhancers but are bound to promoters during mitosis, and we show that this binding is required for appropriate reactivation of bound genes after mitotic exit. Ablation of SMARCE1 during a single mitosis in mouse embryonic stem cells is sufficient to disrupt gene expression, impair the occupancy of several established bookmarks at a subset of their targets and cause aberrant neural differentiation. Thus, SWI/SNF subunit SMARCE1 has a mitotic bookmarking role and is essential for heritable epigenetic fidelity during transcriptional reprogramming.
中文翻译:
SWI/SNF 亚基的有丝分裂书签
为了使细胞启动并维持分化状态,该状态的“记忆”必须通过有丝分裂传递到子细胞1,2,3。哺乳动物开关/蔗糖不可发酵 (SWI/SNF) 复合物(也称为 Brg1/Brg 相关因子或 BAF)通过调节染色质结构来调节基因表达来控制细胞身份 4,5,6,7 ,但它们是否参与细胞命运记忆尚不清楚。在这里,我们提供的证据表明,SWI/SNF 亚基可充当有丝分裂书签,在细胞分裂过程中保护细胞身份。SWI/SNF 核心亚基 SMARCE1 和 SMARCB1 从增强子中被取代,但在有丝分裂期间与启动子结合,并且我们表明这种结合是有丝分裂退出后结合基因的适当重新激活所必需的。在小鼠胚胎干细胞的单次有丝分裂过程中消除 SMARCE1 足以破坏基因表达,损害其目标子集上几个已建立的书签的占用,并导致异常的神经分化。因此,SWI/SNF 亚基 SMARCE1 具有有丝分裂书签作用,对于转录重编程过程中可遗传的表观遗传保真度至关重要。