MyoD is a 3D genome structure organizer for muscle cell identity

• Published in: Nature communications Vol. 13; no. 1; pp. 205 - 17
• Main Authors: Wang, Ruiting, Chen, Fengling, Chen, Qian, Wan, Xin, Shi, Minglei, Chen, Antony K., Ma, Zhao, Li, Guohong, Wang, Min, Ying, Yachen, Liu, Qinyao, Li, Hu, Zhang, Xu, Ma, Jinbiao, Zhong, Jiayun, Chen, Meihong, Zhang, Michael Q., Zhang, Yong, Chen, Yang, Zhu, Dahai
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.01.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 38/32; 38/39; 38/71; 45/15; 631/136/142; 631/337/100/101; 631/532/2439; Animals; Binding Sites; CCCTC-Binding Factor - genetics; CCCTC-Binding Factor - metabolism; Cell Line; Cell lineage; Cell Lineage - genetics; Chromatin; Chromatin Assembly and Disassembly; Chromosomes - chemistry; Chromosomes - metabolism; Gene Expression Regulation, Developmental; Gene Library; Genome; Genomes; Histones - genetics; Histones - metabolism; Humanities and Social Sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; multidisciplinary; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; Muscles; Myoblasts - cytology; Myoblasts - metabolism; MyoD protein; MyoD Protein - genetics; MyoD Protein - metabolism; Myogenin - genetics; Myogenin - metabolism; Myosin Heavy Chains - genetics; Myosin Heavy Chains - metabolism; Protein Binding; Protein Isoforms - genetics; Protein Isoforms - metabolism; Science; Science (multidisciplinary); Signal Transduction; Stem cell transplantation; Stem cells; Transcription factors
• ISSN: 2041-1723; 2041-1723
• 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. Pioneer transcription factors (TFs) have been proposed to act as protein anchors to orchestrate cell type-specific 3D genome architecture. MyoD is a pioneer TF for myogenic lineage specification. Here the authors provide further support for the role of MyoD in 3D genome architecture in muscle stem cells by comparing MyoD knockout and wild-type mice.