哺乳动物ISWI和SWI/SNF选择性介导着不同的转录因子的结合
Darko Barisic1,2,3, Michael B Stadler1,4, Mario Iurlaro1
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Nature
|April 19, 2019
概括
哺乳动物ISWI (SNF2H) 复合体对于核细胞间距和核组织至关重要. 转录因子依赖于特定的染色体重塑剂,如ISWI或SWI/SNF (BRG1),以进行适当的基因组结合.
科学领域:
- 分子生物学
- 基因组学
- 表观遗传学
背景情况:
- 染色体重塑者通过改变核体来管理DNA的可访问性,从而影响基因组的利用.
- 这些复合体在癌症中经常发生变化,但它们在全球核细胞组织中的具体作用尚不清楚.
- 哺乳动物的四个重塑器家族 (SWI/SNF,ISWI,CHD,INO80) 具有不同的功能.
研究的目的:
- 研究SNF2H (ISWI) 的细胞功能,并将其与BRG1 (SWI/SNF) 对比.
- 了解这些重塑者如何协调全球核细胞组织并影响转录因子结合.
主要方法:
- 产生缺乏SNF2H的有生命力的胚胎干细胞.
- 在染色体重塑中对SNF2H和BRG1功能的比较分析.
- 与重塑剂活性相关的转录因子结合的系统分析.
主要成果:
- SNF2H的损失会损害核细胞分相,并增加链接DNA的长度,证实ISWI在核细胞间隔中的作用.
- 特定的转录因子对SNF2H或BRG1的结合有差异性依赖.
- CTCF 结合需要 SNF2H,而 REST 结合则取决于 BRG1.
- SNF2H对于染色体折叠和拓相关域的隔离至关重要.
结论:
- 哺乳动物ISWI复合体对于维持核细胞周期性和核组织至关重要.
- 转录因子利用不同的染色体重塑途径来实现基因组结合的特异性.
- 这项研究阐明了ISWI和SWI/SNF在基因组结构和调节中的具体作用.
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