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Tributyrin, a Butyrate Pro-Drug, Primes Satellite Cells for Differentiation by Altering the Epigenetic Landscape.
- Source :
-
Cells [Cells] 2021 Dec 09; Vol. 10 (12). Date of Electronic Publication: 2021 Dec 09. - Publication Year :
- 2021
-
Abstract
- Satellite 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.
- Subjects :
- Animals
Butyrates chemistry
Butyrates pharmacology
Cell Differentiation drug effects
Cell Differentiation genetics
Chromatin Assembly and Disassembly genetics
Gene Expression Regulation, Developmental drug effects
Histone Deacetylase Inhibitors pharmacology
Hypertrophy genetics
Hypertrophy pathology
Muscle Development drug effects
Muscle Development genetics
Muscle Fibers, Skeletal metabolism
Prodrugs chemistry
Prodrugs pharmacology
RNA, Small Interfering pharmacology
Satellite Cells, Skeletal Muscle metabolism
Swine
Enhancer of Zeste Homolog 2 Protein genetics
MyoD Protein genetics
PAX7 Transcription Factor genetics
Satellite Cells, Skeletal Muscle drug effects
Triglycerides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2073-4409
- Volume :
- 10
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Cells
- Publication Type :
- Academic Journal
- Accession number :
- 34943981
- Full Text :
- https://doi.org/10.3390/cells10123475