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

Ruiting Wang; Fengling Chen; Qian Chen; Xin Wan; Minglei Shi; Antony K Chen; Zhao Ma; Guohong Li; Min Wang; Yachen Ying; Qinyao Liu; Hu Li; Xu Zhang; Jinbiao Ma; Jiayun Zhong; Meihong Chen; Michael Q Zhang; Yong Zhang; Yang Chen; Dahai Zhu

doi:10.1038/s41467-021-27865-6

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

Nat Commun. 2022 Jan 11;13(1):205. doi: 10.1038/s41467-021-27865-6.

Authors

Ruiting Wang^#¹, Fengling Chen^#², Qian Chen^#¹, Xin Wan^#¹, Minglei Shi³, Antony K Chen⁴, Zhao Ma^{4

5}, Guohong Li^{6

7}, Min Wang^{6

7}, Yachen Ying^{4

5}, Qinyao Liu¹, Hu Li^{1

8}, Xu Zhang⁹, Jinbiao Ma¹⁰, Jiayun Zhong¹⁰, Meihong Chen¹, Michael Q Zhang^{11

12

13}, Yong Zhang¹⁴, Yang Chen^{15

16

17}, Dahai Zhu^{18

19}

Affiliations

¹ 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.
² MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Bioinformatics Division, BNRist, Department of Automation, Tsinghua University, 100084, Beijing, China.
³ MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, School of Medicine, Tsinghua University, 100084, Beijing, China.
⁴ Department of Biomedical Engineering, College of Future Technology, Peking University, 100871, Beijing, China.
⁵ Department of Biomedical Engineering, College of Engineering, Peking University, 100871, Beijing, China.
⁶ National Laboratory of Biomacromolecules, CAS Center for Excellent in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, China.
⁷ University of Chinese Academy of Science, 100049, Beijing, China.
⁸ Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), 510320, Guangzhou, China.
⁹ Beijing institute of collaborative innovation, 100094, Beijing, China.
¹⁰ State Key Laboratory of Genetic Engineering, Department of Biochemistry, School of Life Sciences, Fudan University, 200438, Shanghai, China.
¹¹ MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Bioinformatics Division, BNRist, Department of Automation, Tsinghua University, 100084, Beijing, China. michaelzhang@mail.tsinghua.edu.cn.
¹² MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, School of Medicine, Tsinghua University, 100084, Beijing, China. michaelzhang@mail.tsinghua.edu.cn.
¹³ Department of Biological Sciences, Center for Systems Biology, The University of Texas, Dallas 800 West Campbell Road, RL11, Richardson, TX, 75080-3021, USA. michaelzhang@mail.tsinghua.edu.cn.
¹⁴ 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. yongzhang@ibms.pumc.edu.cn.
¹⁵ 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. yc@ibms.pumc.edu.cn.
¹⁶ MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Bioinformatics Division, BNRist, Department of Automation, Tsinghua University, 100084, Beijing, China. yc@ibms.pumc.edu.cn.
¹⁷ MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, School of Medicine, Tsinghua University, 100084, Beijing, China. yc@ibms.pumc.edu.cn.
¹⁸ 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. dhzhu@pumc.edu.cn.
¹⁹ Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), 510320, Guangzhou, China. dhzhu@pumc.edu.cn.

^# Contributed equally.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Binding Sites
CCCTC-Binding Factor / genetics
CCCTC-Binding Factor / metabolism
Cell Line
Cell Lineage / genetics
Chromatin Assembly and Disassembly
Chromosomes / chemistry
Chromosomes / metabolism
Gene Expression Regulation, Developmental
Gene Library
Genome*
Histones / genetics*
Histones / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Muscle, Skeletal / cytology
Muscle, Skeletal / metabolism*
MyoD Protein / genetics*
MyoD Protein / metabolism
Myoblasts / cytology
Myoblasts / metabolism*
Myogenin / genetics
Myogenin / metabolism
Myosin Heavy Chains / genetics
Myosin Heavy Chains / metabolism
Protein Binding
Protein Isoforms / genetics
Protein Isoforms / metabolism
Signal Transduction

Substances

CCCTC-Binding Factor
Histones
Myh3 protein, mouse
MyoD Protein
MyoD1 myogenic differentiation protein
Myog protein, mouse
Myogenin
Protein Isoforms
Myosin Heavy Chains