Muscle progenitor specification and myogenic differentiation are associated with changes in chromatin topology

Nan Zhang, Julen Mendieta-Esteban, Alessandro Magli, Karin C. Lilja, Rita C. R. Perlingeiro, Marc A. Marti-Renom, Aristotelis Tsirigos and Brian David Dynlacht ()
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Nan Zhang: New York University School of Medicine
Julen Mendieta-Esteban: CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)
Alessandro Magli: Lillehei Heart Institute, University of Minnesota
Karin C. Lilja: New York University School of Medicine
Rita C. R. Perlingeiro: Lillehei Heart Institute, University of Minnesota
Marc A. Marti-Renom: CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)
Aristotelis Tsirigos: New York University School of Medicine
Brian David Dynlacht: New York University School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-19999-w

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