美国圣裘德儿童研究医院Charles W. M. Roberts等研究人员合作揭示SWI/SNF亚基的有丝分裂书签作用。相关论文于2023年5月24日发表在《自然》杂志上。

研究人员提供证据表明，SWI/SNF（switch/sucrose non-fermentable）的亚基在细胞分裂过程中作为有丝分裂的书签来保护细胞的特性。SWI/SNF的核心亚单位SMARCE1和SMARCB1在有丝分裂过程中从增强子中移出，但与启动子结合，结果表明这种结合是有丝分裂退出后适当重新激活结合基因所需的。在小鼠胚胎干细胞的一次有丝分裂过程中，SMARCE1的敲低足以破坏基因表达，损害几个已建立的书签在其目标亚群的占用，并导致异常的神经分化。因此，SWI/SNF亚基SMARCE1具有有丝分裂书签的作用，对转录重编程过程中可遗传的表观遗传保真度至关重要。

据了解，要使细胞开始并维持分化状态，必须通过有丝分裂将这种状态的“记忆”传递给子细胞。哺乳动物的SWI/SNF复合物（也被称为Brg1/Brg相关因子，或BAF）通过调节染色质结构来控制细胞身份来调节基因表达，但它们是否参与细胞命运记忆还不清楚。

附：英文原文

Title: Mitotic bookmarking by SWI/SNF subunits

Author: Zhu, Zhexin, Chen, Xiaolong, Guo, Ao, Manzano, Trishabelle, Walsh, Patrick J., Wills, Kendall M., Halliburton, Rebecca, Radko-Juettner, Sandi, Carter, Raymond D., Partridge, Janet F., Green, Douglas R., Zhang, Jinghui, Roberts, Charles W. M.

Issue&Volume: 2023-05-24

Abstract: 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.

DOI: 10.1038/s41586-023-06085-6

Source: https://www.nature.com/articles/s41586-023-06085-6