Tributyrin, a Butyrate Pro-Drug, Primes Satellite Cells for Differentiation by Altering the Epigenetic Landscape

dc.contributor.authorMurray, Robert L.
dc.contributor.authorZhang, Wei
dc.contributor.authorLiu, Jianan
dc.contributor.authorCooper, Jason
dc.contributor.authorMitchell, Alex
dc.contributor.authorBuman, Maria
dc.contributor.authorSong, Jiuzhou
dc.contributor.authorStahl, Chad H.
dc.date.accessioned2023-10-27T18:55:45Z
dc.date.available2023-10-27T18:55:45Z
dc.date.issued2021-12-09
dc.description.abstractSatellite cells (SC) are a population of muscle resident stem cells that are responsible for postnatal muscle growth and repair. With investigation into the genomic regulation of SC fate, the role of the epigenome in governing SC myogenesis is becoming clearer. Histone deacetylase (HDAC) inhibitors have been demonstrated to be effective at enhancing the myogenic program of SC, but their role in altering the epigenetic landscape of SC remains undetermined. Our objective was to determine how an HDAC inhibitor, butyrate, promotes myogenic differentiation. SC from tributyrin treated neonatal piglets showed a decrease relative to SC from control animals in the expression of enhance of zeste homologue-2 (EZH2), a chromatin modifier, ex vivo. Chromatin Immunoprecipitation-Sequencing (ChIP-Seq) analysis of SC isolated from tributyrin treated pigs showed a global reduction of the tri-methylation of lysine 27 of histone H3 (H3K27me3) repressive chromatin mark. To determine if reductions in EZH2 was the primary mechanism through which butyrate affects SC behavior, SC were transfected with siRNA targeting EZH2, treated with 0.5 mM butyrate, or both. Treatment with butyrate reduced paired-box-7 (Pax7) and myogenic differentiation-1 (MyoD) gene expression, while siRNA caused reductions in EZH2 had no effect on their expression. EZH2 depletion did result in an increase in differentiating SC, but not in myotube hypertrophy. These results indicate that while EZH2 reduction may force myogenic differentiation, butyrate may operate through a parallel mechanism to enhance the myogenic program.
dc.description.urihttps://doi.org/10.3390/cells10123475
dc.identifierhttps://doi.org/10.13016/dspace/zoz3-phot
dc.identifier.citationMurray, R.L.; Zhang, W.; Liu, J.; Cooper, J.; Mitchell, A.; Buman, M.; Song, J.; Stahl, C.H. Tributyrin, a Butyrate Pro-Drug, Primes Satellite Cells for Differentiation by Altering the Epigenetic Landscape. Cells 2021, 10, 3475.
dc.identifier.urihttp://hdl.handle.net/1903/31170
dc.language.isoen_US
dc.publisherMDPI
dc.relation.isAvailableAtCollege of Agriculture & Natural Resourcesen_us
dc.relation.isAvailableAtAnimal & Avian Sciencesen_us
dc.relation.isAvailableAtDigital Repository at the University of Marylanden_us
dc.relation.isAvailableAtUniversity of Maryland (College Park, MD)en_us
dc.subjectsatellite cell
dc.subjectbutyrate
dc.subjectepigenetics
dc.subjectChIP-Seq
dc.subjectdifferentiation
dc.subjectHDAC inhibitor
dc.titleTributyrin, a Butyrate Pro-Drug, Primes Satellite Cells for Differentiation by Altering the Epigenetic Landscape
dc.typeArticle
local.equitableAccessSubmissionNo

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