瑞士弗里德里希·米歇尔生物医学研究所Dirk Schübeler团队的研究显示，ISWI亚单位的系统评估表明，NURF为CTCF创造了局部可达性。相关论文于2024年5月30日发表在《自然—遗传学》杂志上。

据悉，模拟开关(ISWI) 家族重塑因子的催化活性，对于核小体组织和某些转录因子(包括绝缘子蛋白CTCF)的DNA结合至关重要。

课题组人员通过一组同源小鼠干细胞系来定义单个亚复合物的贡献，每个干细胞系都缺失六个ISWI辅助亚基中的一个。CERF、RSF、ACF、WICH或NoRC亚复合物亚基的单个缺失仅对染色质图谱产生适度影响，而NURF特异性亚基BPTF的去除会导致，染色质可及性和CTCF位点周围SNF2HATPase定位的显著减少。这影响相邻核小体的占用和CTCF的结合。

在染色质可及性降低的一组位点上，CTCF结合仍然存在，但cohesin占据减少，导致绝缘降低。这些结果表明，CTCF结合可以从其在细胞核组织中的绝缘体功能中分离出来，并确定了NURF在介导SNF2H定位和结合CTCF位点打开染色质方面的特定作用。

附：英文原文

Title: Systematic assessment of ISWI subunits shows that NURF creates local accessibility for CTCF

Author: Iurlaro, Mario, Masoni, Francesca, Flyamer, Ilya M., Wirbelauer, Christiane, Iskar, Murat, Burger, Lukas, Giorgetti, Luca, Schbeler, Dirk

Issue&Volume: 2024-05-30

Abstract: Catalytic activity of the imitation switch (ISWI) family of remodelers is critical for nucleosomal organization and DNA binding of certain transcription factors, including the insulator protein CTCF. Here we define the contribution of individual subcomplexes by deriving a panel of isogenic mouse stem cell lines, each lacking one of six ISWI accessory subunits. Individual deletions of subunits of either CERF, RSF, ACF, WICH or NoRC subcomplexes only moderately affect the chromatin landscape, while removal of the NURF-specific subunit BPTF leads to a strong reduction in chromatin accessibility and SNF2H ATPase localization around CTCF sites. This affects adjacent nucleosome occupancy and CTCF binding. At a group of sites with reduced chromatin accessibility, CTCF binding persists but cohesin occupancy is reduced, resulting in decreased insulation. These results suggest that CTCF binding can be separated from its function as an insulator in nuclear organization and identify a specific role for NURF in mediating SNF2H localization and chromatin opening at bound CTCF sites.

DOI: 10.1038/s41588-024-01767-x

Source: https://www.nature.com/articles/s41588-024-01767-x