Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
Nucleic Acids Res. 2023 Jul 21;51(13):6784-6805. doi: 10.1093/nar/gkad401.
One bottleneck in understanding the principles of 3D chromatin structures is caused by the paucity of known regulators. Cohesin is essential for 3D chromatin organization, and its interacting partners are candidate regulators. Here, we performed proteomic profiling of the cohesin in chromatin and identified transcription factors, RNA-binding proteins and chromatin regulators associated with cohesin. Acute protein degradation followed by time-series genomic binding quantitation and BAT Hi-C analysis were conducted, and the results showed that the transcription factor ZBTB21 contributes to cohesin chromatin binding, 3D chromatin interactions and transcriptional repression. Strikingly, multiomic analyses revealed that the other four ZBTB factors interacted with cohesin, and double degradation of ZBTB21 and ZBTB7B led to a further decrease in cohesin chromatin occupancy. We propose that multiple ZBTB transcription factors orchestrate the chromatin binding of cohesin to regulate chromatin interactions, and we provide a catalog of many additional proteins associated with cohesin that warrant further investigation.
理解三维染色质结构原理的一个瓶颈是已知调控因子的缺乏。黏合蛋白对于三维染色质组织至关重要，其相互作用的伙伴是候选调控因子。在这里，我们对染色质中的黏合蛋白进行了蛋白质组学分析，鉴定出与黏合蛋白相关的转录因子、RNA 结合蛋白和染色质调控因子。随后进行了急性蛋白质降解和时间序列基因组结合定量以及 BAT Hi-C 分析，结果表明转录因子 ZBTB21 有助于黏合蛋白与染色质结合、三维染色质相互作用和转录抑制。引人注目的是，多组学分析表明其他四个 ZBTB 因子与黏合蛋白相互作用，并且 ZBTB21 和 ZBTB7B 的双重降解导致黏合蛋白在染色质上的占有率进一步降低。我们提出，多个 ZBTB 转录因子协调黏合蛋白与染色质的结合，以调节染色质相互作用，并且我们提供了一个与黏合蛋白相关的许多其他蛋白质的目录，这些蛋白质值得进一步研究。
Zotero 插件
