The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, 100005, Beijing, China.
MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Bioinformatics Division, BNRist, Department of Automation, Tsinghua University, 100084, Beijing, China.
Nat Commun. 2022 Jan 11;13(1):205. doi: 10.1038/s41467-021-27865-6.
The genome exists as an organized, three-dimensional (3D) dynamic architecture, and each cell type has a unique 3D genome organization that determines its cell identity. An unresolved question is how cell type-specific 3D genome structures are established during development. Here, we analyzed 3D genome structures in muscle cells from mice lacking the muscle lineage transcription factor (TF), MyoD, versus wild-type mice. We show that MyoD functions as a "genome organizer" that specifies 3D genome architecture unique to muscle cell development, and that H3K27ac is insufficient for the establishment of MyoD-induced chromatin loops in muscle cells. Moreover, we present evidence that other cell lineage-specific TFs might also exert functional roles in orchestrating lineage-specific 3D genome organization during development.
基因组以一种有组织的、三维(3D)动态结构存在,每种细胞类型都有其独特的 3D 基因组组织,决定其细胞身份。一个悬而未决的问题是,细胞类型特异性的 3D 基因组结构如何在发育过程中建立。在这里,我们分析了缺乏肌肉谱系转录因子(TF)MyoD 的小鼠与野生型小鼠的肌肉细胞中的 3D 基因组结构。我们表明,MyoD 作为“基因组组织者”发挥作用,指定了肌肉细胞发育所特有的 3D 基因组结构,而 H3K27ac 不足以在肌肉细胞中建立 MyoD 诱导的染色质环。此外,我们提供的证据表明,其他细胞谱系特异性 TF 也可能在发育过程中发挥功能作用,以协调谱系特异性 3D 基因组组织。