转录因子网络不成比例地丰富了血液细胞表型的遗传性
Jorge Diego Martin-Rufino1,2,3, Alexis Caulier1,2,3, Seayoung Lee2,3
1Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
bioRxiv : the preprint server for biology
|September 24, 2024
概括
与血液特征相关的遗传变异在特定的调节性DNA区域中发现. 一种名为Perturb-multiome的新方法揭示了这些区域是由主转录因子 (TF) 控制的,这显著影响了遗传性.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 血液形成 血液形成 血液形成
背景情况:
- 大多数影响人类特征的遗传变异都位于非编码基因组区域.
- 与血细胞表型相关的变异在血液形成 (血液形成) 期间活跃的调节区域中特别丰富.
研究的目的:
- 系统地研究参与血液形成的调节区域的性质和功能.
- 了解主转录因子 (TFs) 在将遗传变异与基因表达和血细胞表型联系中的作用.
主要方法:
- 开发Perturb-multiome,一个高通量单细胞战略.
- 同时分析染色质可访问性和基因表达.
- 在血液形成分化过程中,主转录因子 (TFs) 的CRISPR介导扰乱.
主要成果:
- 确定了对TF敏感的可访问的染色体区域.
- 这些区域,包括<0.3%的基因组,显示血细胞表型的遗传性~100倍丰富.
- 证明了TFs,可访问的染色体和在血液构成分化中基因表达之间的强烈联系.
结论:
- TF敏感的可访问色素区域是表型相关遗传变异的关键热点.
- 帕特尔布多基组方法通过将cis调节元素与基因调节网络中的向基因联系起来,使得基因变异的大规模机械研究成为可能.
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