美国宾夕法尼亚大学Eric F. Joyce小组在研究中取得进展。他们发现，黏连蛋白促进随机结构域混合以确保边界近端基因的正确调控。相关论文于2020年6月22日在线发表在《自然—遗传学》杂志上。
Title: Cohesin promotes stochastic domain intermingling to ensure proper regulation of boundary-proximal genes
Author: Jennifer M. Luppino, Daniel S. Park, Son C. Nguyen, Yemin Lan, Zhuxuan Xu, Rebecca Yunker, Eric F. Joyce
Abstract: The human genome can be segmented into topologically associating domains (TADs), which have been proposed to spatially sequester genes and regulatory elements through chromatin looping. Interactions between TADs have also been suggested, presumably because of variable boundary positions across individual cells. However, the nature, extent and consequence of these dynamic boundaries remain unclear. Here, we combine high-resolution imaging with Oligopaint technology to quantify the interaction frequencies across both weak and strong boundaries. We find that chromatin intermingling across population-defined boundaries is widespread but that the extent of permissibility is locus-specific. Cohesin depletion, which abolishes domain formation at the population level, does not induce ectopic interactions but instead reduces interactions across all boundaries tested. In contrast, WAPL or CTCF depletion increases inter-domain contacts in a cohesin-dependent manner. Reduced chromatin intermingling due to cohesin loss affects the topology and transcriptional bursting frequencies of genes near boundaries. We propose that cohesin occasionally bypasses boundaries to promote incorporation of boundary-proximal genes into neighboring domains. A combination of super-resolution microscopy and Oligopaint technology shows that TAD boundaries are variable at the single-cell level. Loss of cohesin, in contrast to WAPL or CTCF depletion, reduces interactions across boundaries and alters transcriptional bursting of genes near boundaries.