人类细胞中的转录因子结合发生在围绕着黏合素锚定位点形成的密集簇中。

Transcription factor binding in human cells occurs in dense clusters formed around cohesin anchor sites.

机构信息

Science for Life Laboratory, Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm 14183, Sweden.

出版信息

Cell. 2013 Aug 15;154(4):801-13. doi: 10.1016/j.cell.2013.07.034.

Abstract

During cell division, transcription factors (TFs) are removed from chromatin twice, during DNA synthesis and during condensation of chromosomes. How TFs can efficiently find their sites following these stages has been unclear. Here, we have analyzed the binding pattern of expressed TFs in human colorectal cancer cells. We find that binding of TFs is highly clustered and that the clusters are enriched in binding motifs for several major TF classes. Strikingly, almost all clusters are formed around cohesin, and loss of cohesin decreases both DNA accessibility and binding of TFs to clusters. We show that cohesin remains bound in S phase, holding the nascent sister chromatids together at the TF cluster sites. Furthermore, cohesin remains bound to the cluster sites when TFs are evicted in early M phase. These results suggest that cohesin-binding functions as a cellular memory that promotes re-establishment of TF clusters after DNA replication and chromatin condensation.

摘要

在细胞分裂过程中,转录因子 (TFs) 在 DNA 合成和染色体浓缩期间被从染色质上移除两次。TFs 如何在这些阶段之后有效地找到它们的位置一直不清楚。在这里,我们分析了人结直肠癌细胞中表达的 TFs 的结合模式。我们发现 TF 的结合高度聚集,并且这些簇富含几种主要 TF 类别的结合基序。引人注目的是,几乎所有的簇都是围绕着黏合蛋白形成的,而黏合蛋白的缺失会降低 DNA 的可及性和 TF 与簇的结合。我们表明,黏合蛋白在 S 期保持结合,将新合成的姐妹染色单体在 TF 簇位点处保持在一起。此外,当 TF 在早期 M 期被驱逐时,黏合蛋白仍然结合在簇位点上。这些结果表明,黏合蛋白结合作为一种细胞记忆,促进了 DNA 复制和染色质浓缩后 TF 簇的重新建立。

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