Muscle progenitor specification and myogenic differentiation are associated with changes in chromatin topology
| Autor: | Marc A. Marti-Renom, Alessandro Magli, Karin C. Lilja, Rita C.R. Perlingeiro, Julen Mendieta-Esteban, Brian David Dynlacht, Nan Zhang, Aristotelis Tsirigos |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Science Gene regulatory network General Physics and Astronomy Biology Miogènesi Muscle Development General Biochemistry Genetics and Molecular Biology Article Cromatina 03 medical and health sciences Mice 0302 clinical medicine Skeletal muscle cell differentiation 3T3-L1 Cells Myosin Muscle stem cells medicine Animals Humans Gene Regulatory Networks Epigenetics Enhancer Muscle Skeletal Transcription factor Cells Cultured Multidisciplinary Gene Expression Profiling Músculs Skeletal muscle PAX7 Transcription Factor Cell Differentiation Mouse Embryonic Stem Cells General Chemistry musculoskeletal system Chromatin Cell biology 030104 developmental biology medicine.anatomical_structure Gene Ontology Next-generation sequencing Gene expression tissues 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-18 (2020) |
| ISSN: | 2041-1723 |
| Popis: | Using Hi-C, promoter-capture Hi-C (pCHi-C), and other genome-wide approaches in skeletal muscle progenitors that inducibly express a master transcription factor, Pax7, we systematically characterize at high-resolution the spatio-temporal re-organization of compartments and promoter-anchored interactions as a consequence of myogenic commitment and differentiation. We identify key promoter-enhancer interaction motifs, namely, cliques and networks, and interactions that are dependent on Pax7 binding. Remarkably, Pax7 binds to a majority of super-enhancers, and together with a cadre of interacting transcription factors, assembles feed-forward regulatory loops. During differentiation, epigenetic memory and persistent looping are maintained at a subset of Pax7 enhancers in the absence of Pax7. We also identify and functionally validate a previously uncharacterized Pax7-bound enhancer hub that regulates the essential myosin heavy chain cluster during skeletal muscle cell differentiation. Our studies lay the groundwork for understanding the role of Pax7 in orchestrating changes in the three-dimensional chromatin conformation in muscle progenitors. Chromatin structure and topology play important roles in the regulation of gene expression. Here the authors study the spatio-temporal re-organization of promoter-enhancer interactions in pluripotent ES and skeletal muscle stem cells and the corresponding impact on gene expression as a consequence of myogenic commitment and differentiation. |
| Databáze: | OpenAIRE |
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