小柯机器人

美国加州大学Robert Tjian和Xavier Darzacq共同合作，近期取得重要工作进展。他们研究发现，CTCF、黏连蛋白、WAPL或YY1的急性丢失对增强子-启动子相互作用和转录的影响较小。相关研究结果2022年12月5日在线发表于《自然—遗传学》杂志上。

据介绍，尽管CTCF（CCCTC结合因子）和黏连蛋白在结构域和结构环水平上显著干扰了三维（3D）基因组折叠，但它们的急性耗竭却仅轻微影响大多数基因的表达，原因目前尚不清楚。

为了解决这个难题，研究人员在小鼠胚胎干细胞中使用了高分辨率Micro-C和新生转录谱。他们研究发现，增强子-启动子（E–P）相互作用在很大程度上对CTCF、黏连蛋白或WAPL的急性（3小时）耗竭不敏感。YY1被认为是E–P环的结构调节剂，但急性YY1耗竭对E–P循环、转录和3D基因组折叠的影响也很小。引人注目的是，活细胞单分子成像显示，黏连蛋白损耗会减少转录因子（TF）与染色质的结合。

因此，尽管CTCF、黏连蛋白、WAPL或YY1不是大多数E–P相互作用和基因表达的短期维持所必需的，但研究结果表明，黏连蛋白可能有助于TF更有效地搜索并结合其靶点。

附：英文原文

Title: Enhancer–promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1

Author: Hsieh, Tsung-Han S., Cattoglio, Claudia, Slobodyanyuk, Elena, Hansen, Anders S., Darzacq, Xavier, Tjian, Robert

Issue&Volume: 2022-12-05

Abstract: It remains unclear why acute depletion of CTCF (CCCTC-binding factor) and cohesin only marginally affects expression of most genes despite substantially perturbing three-dimensional (3D) genome folding at the level of domains and structural loops. To address this conundrum, we used high-resolution Micro-C and nascent transcript profiling in mouse embryonic stem cells. We find that enhancer–promoter (E–P) interactions are largely insensitive to acute (3-h) depletion of CTCF, cohesin or WAPL. YY1 has been proposed as a structural regulator of E–P loops, but acute YY1 depletion also had minimal effects on E–P loops, transcription and 3D genome folding. Strikingly, live-cell, single-molecule imaging revealed that cohesin depletion reduced transcription factor (TF) binding to chromatin. Thus, although CTCF, cohesin, WAPL or YY1 is not required for the short-term maintenance of most E–P interactions and gene expression, our results suggest that cohesin may facilitate TFs to search for and bind their targets more efficiently.

DOI: 10.1038/s41588-022-01223-8

Source: https://www.nature.com/articles/s41588-022-01223-8

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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