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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.
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.
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1 Peking Union Medical College, The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Beijing, China (GRID:grid.506261.6) (ISNI:0000 0001 0706 7839)
2 Tsinghua University, MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Bioinformatics Division, BNRist, Department of Automation, Beijing, China (GRID:grid.12527.33) (ISNI:0000 0001 0662 3178)
3 Tsinghua University, MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, School of Medicine, Beijing, China (GRID:grid.12527.33) (ISNI:0000 0001 0662 3178)
4 Peking University, Department of Biomedical Engineering, College of Future Technology, Beijing, China (GRID:grid.11135.37) (ISNI:0000 0001 2256 9319)
5 Peking University, Department of Biomedical Engineering, College of Future Technology, Beijing, China (GRID:grid.11135.37) (ISNI:0000 0001 2256 9319); Peking University, Department of Biomedical Engineering, College of Engineering, Beijing, China (GRID:grid.11135.37) (ISNI:0000 0001 2256 9319)
6 Chinese Academy of Sciences, National Laboratory of Biomacromolecules, CAS Center for Excellent in Biomacromolecules, Institute of Biophysics, Beijing, China (GRID:grid.9227.e) (ISNI:0000000119573309); University of Chinese Academy of Science, Beijing, China (GRID:grid.410726.6) (ISNI:0000 0004 1797 8419)
7 Peking Union Medical College, The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Beijing, China (GRID:grid.506261.6) (ISNI:0000 0001 0706 7839); Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, China (GRID:grid.508040.9) (ISNI:0000 0004 9415 435X)
8 Beijing institute of collaborative innovation, Beijing, China (GRID:grid.508040.9)
9 Fudan University, State Key Laboratory of Genetic Engineering, Department of Biochemistry, School of Life Sciences, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443)
10 Tsinghua University, MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Bioinformatics Division, BNRist, Department of Automation, Beijing, China (GRID:grid.12527.33) (ISNI:0000 0001 0662 3178); Tsinghua University, MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, School of Medicine, Beijing, China (GRID:grid.12527.33) (ISNI:0000 0001 0662 3178); The University of Texas, Department of Biological Sciences, Center for Systems Biology, Richardson, USA (GRID:grid.267323.1) (ISNI:0000 0001 2151 7939)
11 Peking Union Medical College, The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Beijing, China (GRID:grid.506261.6) (ISNI:0000 0001 0706 7839); Tsinghua University, MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Bioinformatics Division, BNRist, Department of Automation, Beijing, China (GRID:grid.12527.33) (ISNI:0000 0001 0662 3178); Tsinghua University, MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, School of Medicine, Beijing, China (GRID:grid.12527.33) (ISNI:0000 0001 0662 3178)