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Myogenin is required for assembly of the transcription machinery on muscle genes during skeletal muscle differentiation

Skeletal muscle gene expression is governed by the myogenic regulatory family (MRF) which includes MyoD (MYOD1) and myogenin (MYOG). MYOD1 and MYOG are known to regulate an overlapping set of muscle genes, but MYOD1 cannot compensate for the absence of MYOG in vivo. In vitro, late muscle genes have...

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Autores principales: Adhikari, Abhinav, Kim, William, Davie, Judith
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815108/
https://www.ncbi.nlm.nih.gov/pubmed/33465133
http://dx.doi.org/10.1371/journal.pone.0245618
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author Adhikari, Abhinav
Kim, William
Davie, Judith
author_facet Adhikari, Abhinav
Kim, William
Davie, Judith
author_sort Adhikari, Abhinav
collection PubMed
description Skeletal muscle gene expression is governed by the myogenic regulatory family (MRF) which includes MyoD (MYOD1) and myogenin (MYOG). MYOD1 and MYOG are known to regulate an overlapping set of muscle genes, but MYOD1 cannot compensate for the absence of MYOG in vivo. In vitro, late muscle genes have been shown to be bound by both factors, but require MYOG for activation. The molecular basis for this requirement was unclear. We show here that MYOG is required for the recruitment of TBP and RNAPII to muscle gene promoters, indicating that MYOG is essential in assembling the transcription machinery. Genes regulated by MYOD1 and MYOG include genes required for muscle fusion, myomaker and myomerger, and we show that myomaker is fully dependent on activation by MYOG. We also sought to determine the role of MYOD1 in MYOG dependent gene activation and unexpectedly found that MYOG is required to maintain Myod1 expression. However, we also found that exogenous MYOD1 was unable to compensate for the loss of Myog and activate muscle gene expression. Thus, our results show that MYOD1 and MYOG act in a feed forward loop to maintain each other’s expression and also show that it is MYOG, and not MYOD1, that is required to load TBP and activate gene expression on late muscle gene promoters bound by both factors.
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spelling pubmed-78151082021-01-27 Myogenin is required for assembly of the transcription machinery on muscle genes during skeletal muscle differentiation Adhikari, Abhinav Kim, William Davie, Judith PLoS One Research Article Skeletal muscle gene expression is governed by the myogenic regulatory family (MRF) which includes MyoD (MYOD1) and myogenin (MYOG). MYOD1 and MYOG are known to regulate an overlapping set of muscle genes, but MYOD1 cannot compensate for the absence of MYOG in vivo. In vitro, late muscle genes have been shown to be bound by both factors, but require MYOG for activation. The molecular basis for this requirement was unclear. We show here that MYOG is required for the recruitment of TBP and RNAPII to muscle gene promoters, indicating that MYOG is essential in assembling the transcription machinery. Genes regulated by MYOD1 and MYOG include genes required for muscle fusion, myomaker and myomerger, and we show that myomaker is fully dependent on activation by MYOG. We also sought to determine the role of MYOD1 in MYOG dependent gene activation and unexpectedly found that MYOG is required to maintain Myod1 expression. However, we also found that exogenous MYOD1 was unable to compensate for the loss of Myog and activate muscle gene expression. Thus, our results show that MYOD1 and MYOG act in a feed forward loop to maintain each other’s expression and also show that it is MYOG, and not MYOD1, that is required to load TBP and activate gene expression on late muscle gene promoters bound by both factors. Public Library of Science 2021-01-19 /pmc/articles/PMC7815108/ /pubmed/33465133 http://dx.doi.org/10.1371/journal.pone.0245618 Text en © 2021 Adhikari et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Adhikari, Abhinav
Kim, William
Davie, Judith
Myogenin is required for assembly of the transcription machinery on muscle genes during skeletal muscle differentiation
title Myogenin is required for assembly of the transcription machinery on muscle genes during skeletal muscle differentiation
title_full Myogenin is required for assembly of the transcription machinery on muscle genes during skeletal muscle differentiation
title_fullStr Myogenin is required for assembly of the transcription machinery on muscle genes during skeletal muscle differentiation
title_full_unstemmed Myogenin is required for assembly of the transcription machinery on muscle genes during skeletal muscle differentiation
title_short Myogenin is required for assembly of the transcription machinery on muscle genes during skeletal muscle differentiation
title_sort myogenin is required for assembly of the transcription machinery on muscle genes during skeletal muscle differentiation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815108/
https://www.ncbi.nlm.nih.gov/pubmed/33465133
http://dx.doi.org/10.1371/journal.pone.0245618
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