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GCN5 maintains muscle integrity by acetylating YY1 to promote dystrophin expression

Protein lysine acetylation is a post-translational modification that regulates protein structure and function. It is targeted to proteins by lysine acetyltransferases (KATs) or removed by lysine deacetylases. This work identifies a role for the KAT enzyme general control of amino acid synthesis prot...

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Autores principales: Addicks, Gregory C., Zhang, Hongbo, Ryu, Dongryeol, Vasam, Goutham, Green, Alexander E., Marshall, Philip L., Patel, Sonia, Kang, Baeki E., Kim, Doyoun, Katsyuba, Elena, Williams, Evan G., Renaud, Jean-Marc, Auwerx, Johan, Menzies, Keir J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8931935/
https://www.ncbi.nlm.nih.gov/pubmed/35024765
http://dx.doi.org/10.1083/jcb.202104022
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author Addicks, Gregory C.
Zhang, Hongbo
Ryu, Dongryeol
Vasam, Goutham
Green, Alexander E.
Marshall, Philip L.
Patel, Sonia
Kang, Baeki E.
Kim, Doyoun
Katsyuba, Elena
Williams, Evan G.
Renaud, Jean-Marc
Auwerx, Johan
Menzies, Keir J.
author_facet Addicks, Gregory C.
Zhang, Hongbo
Ryu, Dongryeol
Vasam, Goutham
Green, Alexander E.
Marshall, Philip L.
Patel, Sonia
Kang, Baeki E.
Kim, Doyoun
Katsyuba, Elena
Williams, Evan G.
Renaud, Jean-Marc
Auwerx, Johan
Menzies, Keir J.
author_sort Addicks, Gregory C.
collection PubMed
description Protein lysine acetylation is a post-translational modification that regulates protein structure and function. It is targeted to proteins by lysine acetyltransferases (KATs) or removed by lysine deacetylases. This work identifies a role for the KAT enzyme general control of amino acid synthesis protein 5 (GCN5; KAT2A) in regulating muscle integrity by inhibiting DNA binding of the transcription factor/repressor Yin Yang 1 (YY1). Here we report that a muscle-specific mouse knockout of GCN5 (Gcn5(skm)(−/−)) reduces the expression of key structural muscle proteins, including dystrophin, resulting in myopathy. GCN5 was found to acetylate YY1 at two residues (K392 and K393), disrupting the interaction between the YY1 zinc finger region and DNA. These findings were supported by human data, including an observed negative correlation between YY1 gene expression and muscle fiber diameter. Collectively, GCN5 positively regulates muscle integrity through maintenance of structural protein expression via acetylation-dependent inhibition of YY1. This work implicates the role of protein acetylation in the regulation of muscle health and for consideration in the design of novel therapeutic strategies to support healthy muscle during myopathy or aging.
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spelling pubmed-89319352022-07-14 GCN5 maintains muscle integrity by acetylating YY1 to promote dystrophin expression Addicks, Gregory C. Zhang, Hongbo Ryu, Dongryeol Vasam, Goutham Green, Alexander E. Marshall, Philip L. Patel, Sonia Kang, Baeki E. Kim, Doyoun Katsyuba, Elena Williams, Evan G. Renaud, Jean-Marc Auwerx, Johan Menzies, Keir J. J Cell Biol Article Protein lysine acetylation is a post-translational modification that regulates protein structure and function. It is targeted to proteins by lysine acetyltransferases (KATs) or removed by lysine deacetylases. This work identifies a role for the KAT enzyme general control of amino acid synthesis protein 5 (GCN5; KAT2A) in regulating muscle integrity by inhibiting DNA binding of the transcription factor/repressor Yin Yang 1 (YY1). Here we report that a muscle-specific mouse knockout of GCN5 (Gcn5(skm)(−/−)) reduces the expression of key structural muscle proteins, including dystrophin, resulting in myopathy. GCN5 was found to acetylate YY1 at two residues (K392 and K393), disrupting the interaction between the YY1 zinc finger region and DNA. These findings were supported by human data, including an observed negative correlation between YY1 gene expression and muscle fiber diameter. Collectively, GCN5 positively regulates muscle integrity through maintenance of structural protein expression via acetylation-dependent inhibition of YY1. This work implicates the role of protein acetylation in the regulation of muscle health and for consideration in the design of novel therapeutic strategies to support healthy muscle during myopathy or aging. Rockefeller University Press 2022-01-13 /pmc/articles/PMC8931935/ /pubmed/35024765 http://dx.doi.org/10.1083/jcb.202104022 Text en © 2022 Addicks et al. https://creativecommons.org/licenses/by-nc-sa/4.0/http://www.rupress.org/terms/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Addicks, Gregory C.
Zhang, Hongbo
Ryu, Dongryeol
Vasam, Goutham
Green, Alexander E.
Marshall, Philip L.
Patel, Sonia
Kang, Baeki E.
Kim, Doyoun
Katsyuba, Elena
Williams, Evan G.
Renaud, Jean-Marc
Auwerx, Johan
Menzies, Keir J.
GCN5 maintains muscle integrity by acetylating YY1 to promote dystrophin expression
title GCN5 maintains muscle integrity by acetylating YY1 to promote dystrophin expression
title_full GCN5 maintains muscle integrity by acetylating YY1 to promote dystrophin expression
title_fullStr GCN5 maintains muscle integrity by acetylating YY1 to promote dystrophin expression
title_full_unstemmed GCN5 maintains muscle integrity by acetylating YY1 to promote dystrophin expression
title_short GCN5 maintains muscle integrity by acetylating YY1 to promote dystrophin expression
title_sort gcn5 maintains muscle integrity by acetylating yy1 to promote dystrophin expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8931935/
https://www.ncbi.nlm.nih.gov/pubmed/35024765
http://dx.doi.org/10.1083/jcb.202104022
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