对ISWI子单位的系统评估表明,NURF为CTCF创造了当地可访问性
Mario Iurlaro1,2, Francesca Masoni1,3, Ilya M Flyamer1
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Nature genetics
|May 30, 2024
概括
NURF子单元BPTF对于染色质可访问性和CTCF绝缘体功能至关重要. 它的去除损害了SNF2H局部化,并减少了凝聚力,影响了基因隔离.
科学领域:
- 染色体生物学 染色体生物学
- 分子遗传学 分子遗传学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 模仿开关 (ISWI) 家庭的ATP依赖的染色体重塑剂在核细胞组织中起着至关重要的作用.
- ISWI重塑器对于转录因子的DNA结合至关重要,例如绝缘体蛋白CTCF.
- 了解ISWI亚复合体的特定作用是阐明它们在基因调节中的功能的关键.
研究的目的:
- 划分ISWI配件子单元对染色体组织和CTCF介导绝缘的贡献.
- 调查亚单元枯竭对染色质可访问性,核细胞占用率和CTCF位点蛋白质局部化的影响.
主要方法:
- 产生异构的小鼠干细胞系,具有特定的ISWI辅助子单元缺失.
- 染色体可访问性测定和SNF2H和凝聚性的ChIP-seq.
- 对核细胞占用率和在目标部位的CTCF结合的分析.
主要成果:
- 删除大多数ISWI辅助子单元对染色体景观产生了轻微的影响.
- 对NURF特异性子单元BPTF的损失显著降低了CTCF位点周围的染色质可访问性和SNF2H ATPase局部化.
- 在一些可访问性降低的地点,CTCF结合仍然存在,但凝聚体占用率下降,导致隔热受损.
结论:
- 在功能上可以将CTCF结合与其作为绝缘体的作用分开.
- NURF复合体,特别是BPTF,在调解SNF2H局部化和CTCF结合部位的染色质开放方面发挥着关键作用.
- 这突出了ISWI改造者调节绝缘体功能和核组织的特定机制.
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