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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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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. |
format | Online Article Text |
id | pubmed-7815108 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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