Disruption of Smarce1, a component of the SWI/SNF chromatin remodeling complex, decreases nucleosome stability in mouse embryonic stem cells and impairs differentiation
Disruption of Smarce1, a component of the SWI/SNF chromatin remodeling complex, decreases nucleosome stability in mouse embryonic stem cells and impairs differentiation
复制标题
Smarce1（SWI/SNF 染色质重塑复合物的一个组成部分）的破坏会降低小鼠胚胎干细胞的核小体稳定性并损害分化
DOI：
10.1101/2022.05.18.492397
复制
发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Kyoji Horie
中科院分区：
文献类型：
--
作者：
Katsunobu Kashiwagi;Junko Yoshida;Hiroshi Kimura;Kyoji Horie
SWI/SNF染色质重塑复合物由超过10种组分蛋白组成，形成> 1 MDa的大蛋白复合物。催化蛋白Smarca 4或Smarca 2与组分蛋白协同工作，形成适合于转录调控的染色质平台。然而，每种组分蛋白与催化蛋白协同作用的机制在很大程度上仍然未知。在这里，我们报告的Smarce 1，SWI/SNF复合物的组成部分，通过纯合突变胚胎干细胞（ES）的表型分析的功能。Smarce 1的破坏诱导了SWI/SNF复合物中其他复合物组分的解离。组蛋白与DNA的结合在纯合突变ES细胞中松动，表明Smarce 1的破坏降低了核小体的稳定性。蔗糖梯度沉降分析表明SWI/SNF复合物的异位基因组分布，占染色质构象的失调。不稳定的核小体仍然在ES细胞分化，损害异染色质形成的分化过程中的特点。这些结果表明Smarce 1引导SWI/SNF复合物到适当的基因组区域，以产生足以进行转录调控的染色质结构。
The SWI/SNF chromatin remodeling complex consists of more than 10 component proteins that form a large protein complex of > 1 MDa. The catalytic proteins Smarca4 or Smarca2 work in concert with the component proteins to form a chromatin platform suitable for transcriptional regulation. However, the mechanism by which each component protein works synergistically with the catalytic proteins remains largely unknown. Here, we report on the function of Smarce1, a component of the SWI/SNF complex, through the phenotypic analysis of homozygous mutant embryonic stem (ES) cells. Disruption of Smarce1 induced the dissociation of other complex components from the SWI/SNF complex. Histone binding to DNA was loosened in homozygous mutant ES cells, indicating that disruption of Smarce1 decreased nucleosome stability. Sucrose gradient sedimentation analysis suggested an ectopic genomic distribution of the SWI/SNF complex, accounting for the misregulation of chromatin conformations. Unstable nucleosomes remained during ES cell differentiation, impairing the heterochromatin formation that is characteristic of the differentiation process. These results suggest that Smarce1 guides the SWI/SNF complex to the appropriate genomic regions to generate chromatin structures adequate for transcriptional regulation.
登录
查看更多内容
影响因子：
16
作者：
Cao, R;Zhang, Y
通讯作者：
Zhang, Y
影响因子：
7.2
作者：
Becker, Peter B.;Workman, Jerry L.
通讯作者：
Workman, Jerry L.
通过MOZ和DPF2的双PHD手指对组蛋白共同识别的选择性识别。
影响因子：
14.8
作者：
Xiong X;Panchenko T;Yang S;Zhao S;Yan P;Zhang W;Xie W;Li Y;Zhao Y;Allis CD;Li H
通讯作者：
Li H
影响因子：
--
作者：
K. Ura;Y. Kaneda
通讯作者：
Y. Kaneda
影响因子：
30.8
作者：
Kadoch C;Williams RT;Calarco JP;Miller EL;Weber CM;Braun SM;Pulice JL;Chory EJ;Crabtree GR
通讯作者：
Crabtree GR