全基因组转录因子结合图揭示了人类HSPCs调控结构的细胞特异性变化
Shruthi Subramanian1, Julie A I Thoms2, Yizhou Huang3
1School of Clinical Medicine, University of New South Wales, Sydney, Australia.
这项研究揭示了转录因子 (TFs) 的特定组合如何从造血干细胞和原生细胞 (HSPCs) 调节血细胞的发育. 这些TF组合主要是调节元素,指导细胞分化,并提供有关血液疾病的见解.
科学领域:
- 血液形成的研究研究.
- 表观遗传学和基因调控
- 细胞和分子生物学 细胞和分子生物学
背景情况:
- 通过复杂的转录因子 (TF) 相互作用,血造干细胞和原始细胞 (HSPC) 分化为成熟的血细胞.
- 众所周知,一组特定的七个TFs,heptad,在HSPC中绑定了监管元素,但它们的独特作用尚不清楚.
研究的目的:
- 研究在人类HSPC分组中特定的heptad-TF组合的全基因组结合模式和调控作用.
- 了解这些TF组合如何影响细胞类型特异性基因表达和造血分化.
主要方法:
- 染色体接触 (HiC,HiChIP) 和修饰 (H3K27ac,H3K4me3,H3K27me3) 的全基因组映射.
- 在各个HSPC亚群中对10个TF结合点 (heptad TFs,PU.1,CTCF,STAG2) 的分析.
- 对增强剂-促进剂相互作用和TF结合动机语法的分析.
主要成果:
- 跨HSPC子组的TF占用率和增强剂-促进剂相互作用的显著变化,与细胞类型特定的基因表达相关.
- 识别与干细胞特异性,骨髓特异性和红细胞特异性调节元素相关的独特的heptad-TF组合.
- 证明heptad占据的地区随后受到界定血统的TF的约束,这表明了它们的初始作用.
结论:
- 在人类的HSPC中,Heptad-TF复合体表现出细胞类型特定的结合和调控功能.
- 组合型TF结合受DNA序列动机的影响,为基因调节提供"语法".
- 这项研究为了解成人血液形成和白血病异常调节网络提供了全面的资源.
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