Six1 promotes skeletal muscle thyroid hormone response through regulation of the MCT10 transporter

Abstract Background The Six1 transcription factor is implicated in controlling the development of several tissue types, notably skeletal muscle. Six1 also contributes to muscle metabolism and its activity is associated with the fast-twitch, glycolytic phenotype. Six1 regulates the expression of cert...

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Autores principales:	John Girgis, Dabo Yang, Imane Chakroun, Yubing Liu, Alexandre Blais
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Diseases of the musculoskeletal system RC925-935
Acceso en línea:	https://doaj.org/article/0290862a482541488d9701f6c4b47c5e
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spelling	oai:doaj.org-article:0290862a482541488d9701f6c4b47c5e2021-11-28T12:05:27ZSix1 promotes skeletal muscle thyroid hormone response through regulation of the MCT10 transporter10.1186/s13395-021-00281-62044-5040https://doaj.org/article/0290862a482541488d9701f6c4b47c5e2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13395-021-00281-6https://doaj.org/toc/2044-5040Abstract Background The Six1 transcription factor is implicated in controlling the development of several tissue types, notably skeletal muscle. Six1 also contributes to muscle metabolism and its activity is associated with the fast-twitch, glycolytic phenotype. Six1 regulates the expression of certain genes of the fast muscle program by directly stimulating their transcription or indirectly acting through a long non-coding RNA. We hypothesized that additional mechanisms of action of Six1 might be at play. Methods A combined analysis of gene expression profiling and genome-wide location analysis data was performed. Results were validated using in vivo RNA interference loss-of-function assays followed by measurement of gene expression by RT-PCR and transcriptional reporter assays. Results The Slc16a10 gene, encoding the thyroid hormone transmembrane transporter MCT10, was identified as a gene with a transcriptional enhancer directly bound by Six1 and requiring Six1 activity for full expression in adult mouse tibialis anterior, a predominantly fast-twitch muscle. Of the various thyroid hormone transporters, MCT10 mRNA was found to be the most abundant in skeletal muscle, and to have a stronger expression in fast-twitch compared to slow-twitch muscle groups. Loss-of-function of MCT10 in the tibialis anterior recapitulated the effect of Six1 on the expression of fast-twitch muscle genes and led to lower activity of a thyroid hormone receptor-dependent reporter gene. Conclusions These results shed light on the molecular mechanisms controlling the tissue expression profile of MCT10 and identify modulation of the thyroid hormone signaling pathway as an additional mechanism by which Six1 influences skeletal muscle metabolism.John GirgisDabo YangImane ChakrounYubing LiuAlexandre BlaisBMCarticleDiseases of the musculoskeletal systemRC925-935ENSkeletal Muscle, Vol 11, Iss 1, Pp 1-21 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diseases of the musculoskeletal system RC925-935
spellingShingle	Diseases of the musculoskeletal system RC925-935 John Girgis Dabo Yang Imane Chakroun Yubing Liu Alexandre Blais Six1 promotes skeletal muscle thyroid hormone response through regulation of the MCT10 transporter
description	Abstract Background The Six1 transcription factor is implicated in controlling the development of several tissue types, notably skeletal muscle. Six1 also contributes to muscle metabolism and its activity is associated with the fast-twitch, glycolytic phenotype. Six1 regulates the expression of certain genes of the fast muscle program by directly stimulating their transcription or indirectly acting through a long non-coding RNA. We hypothesized that additional mechanisms of action of Six1 might be at play. Methods A combined analysis of gene expression profiling and genome-wide location analysis data was performed. Results were validated using in vivo RNA interference loss-of-function assays followed by measurement of gene expression by RT-PCR and transcriptional reporter assays. Results The Slc16a10 gene, encoding the thyroid hormone transmembrane transporter MCT10, was identified as a gene with a transcriptional enhancer directly bound by Six1 and requiring Six1 activity for full expression in adult mouse tibialis anterior, a predominantly fast-twitch muscle. Of the various thyroid hormone transporters, MCT10 mRNA was found to be the most abundant in skeletal muscle, and to have a stronger expression in fast-twitch compared to slow-twitch muscle groups. Loss-of-function of MCT10 in the tibialis anterior recapitulated the effect of Six1 on the expression of fast-twitch muscle genes and led to lower activity of a thyroid hormone receptor-dependent reporter gene. Conclusions These results shed light on the molecular mechanisms controlling the tissue expression profile of MCT10 and identify modulation of the thyroid hormone signaling pathway as an additional mechanism by which Six1 influences skeletal muscle metabolism.
format	article
author	John Girgis Dabo Yang Imane Chakroun Yubing Liu Alexandre Blais
author_facet	John Girgis Dabo Yang Imane Chakroun Yubing Liu Alexandre Blais
author_sort	John Girgis
title	Six1 promotes skeletal muscle thyroid hormone response through regulation of the MCT10 transporter
title_short	Six1 promotes skeletal muscle thyroid hormone response through regulation of the MCT10 transporter
title_full	Six1 promotes skeletal muscle thyroid hormone response through regulation of the MCT10 transporter
title_fullStr	Six1 promotes skeletal muscle thyroid hormone response through regulation of the MCT10 transporter
title_full_unstemmed	Six1 promotes skeletal muscle thyroid hormone response through regulation of the MCT10 transporter
title_sort	six1 promotes skeletal muscle thyroid hormone response through regulation of the mct10 transporter
publisher	BMC
publishDate	2021
url	https://doaj.org/article/0290862a482541488d9701f6c4b47c5e
work_keys_str_mv	AT johngirgis six1promotesskeletalmusclethyroidhormoneresponsethroughregulationofthemct10transporter AT daboyang six1promotesskeletalmusclethyroidhormoneresponsethroughregulationofthemct10transporter AT imanechakroun six1promotesskeletalmusclethyroidhormoneresponsethroughregulationofthemct10transporter AT yubingliu six1promotesskeletalmusclethyroidhormoneresponsethroughregulationofthemct10transporter AT alexandreblais six1promotesskeletalmusclethyroidhormoneresponsethroughregulationofthemct10transporter
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Six1 promotes skeletal muscle thyroid hormone response through regulation of the MCT10 transporter

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