小柯机器人

CRISPR和生化筛选表明MAZ是CTCF介导的Hox簇绝缘的辅助因子
2022-02-13 21:37

美国纽约大学格罗斯曼医学院Danny Reinberg研究团队近期取得一项新突破。他们通过联合使用CRISPR和生化筛选方法,发现MAZ是CTCF介导的Hox簇绝缘活性中的辅助因子。相关论文于2022年2月10日发表在《自然—遗传学》杂志上。

在这里,研究人员进行了全基因组 CRISPR 敲除筛选,以识别HoxA簇的CTCF绝缘活性所需的基因,并辅以生化方法。在候选基因中,研究人员将Myc相关锌指蛋白(MAZ)确定为CTCF绝缘活性的辅助因子。MAZ在染色质边界与CTCF共定位,并且跟CTCF类似,与粘连素亚基RAD21相互作用。MAZ敲除破坏了拓扑关联区域内的基因表达和局部接触。与CTCF基序缺失类似,MAZ基序缺失导致分化后CTCF边界Hox基因立即去抑制,从而引起小鼠的同源性转化。因此,MAZ是在发育过程中有助于适当绝缘、基因表达和基因组结构的一个因素。

据介绍,CCCTC 结合因子 (CTCF) 对基因组三维结构形成至关重要。 在分化过程中,CTCF能将Hox基因簇内的活性和抑制基因隔离绝缘开来。

附:英文原文

Title: CRISPR and biochemical screens identify MAZ as a cofactor in CTCF-mediated insulation at Hox clusters

Author: Ortabozkoyun, Havva, Huang, Pin-Yao, Cho, Hyunwoo, Narendra, Varun, LeRoy, Gary, Gonzalez-Buendia, Edgar, Skok, Jane A., Tsirigos, Aristotelis, Mazzoni, Esteban O., Reinberg, Danny

Issue&Volume: 2022-02-10

Abstract: CCCTC-binding factor (CTCF) is critical to three-dimensional genome organization. Upon differentiation, CTCF insulates active and repressed genes within Hox gene clusters. We conducted a genome-wide CRISPR knockout (KO) screen to identify genes required for CTCF-boundary activity at the HoxA cluster, complemented by biochemical approaches. Among the candidates, we identified Myc-associated zinc-finger protein (MAZ) as a cofactor in CTCF insulation. MAZ colocalizes with CTCF at chromatin borders and, similar to CTCF, interacts with the cohesin subunit RAD21. MAZ KO disrupts gene expression and local contacts within topologically associating domains. Similar to CTCF motif deletions, MAZ motif deletions lead to derepression of posterior Hox genes immediately after CTCF boundaries upon differentiation, giving rise to homeotic transformations in mouse. Thus, MAZ is a factor contributing to appropriate insulation, gene expression and genomic architecture during development. Genome-wide screens identify several genes, including MAZ, required for CTCF-mediated insulation. MAZ interacts with cohesin, and MAZ motif deletions derepress posterior Hox gene expression, leading to homeotic transformations in mouse.

DOI: 10.1038/s41588-021-01008-5

Source: https://www.nature.com/articles/s41588-021-01008-5#Sec2

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
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

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