HDAC4 regulates satellite cell proliferation and differentiation by targeting P21 and Sharp1 genes

Scientific Reports
Nicoletta MarroncelliViviana Moresi

Abstract

Skeletal muscle exhibits a high regenerative capacity, mainly due to the ability of satellite cells to replicate and differentiate in response to appropriate stimuli. Epigenetic control is effective at different stages of this process. It has been shown that the chromatin-remodeling factor HDAC4 is able to regulate satellite cell proliferation and commitment. However, its molecular targets are still uncovered. To explain the signaling pathways regulated by HDAC4 in satellite cells, we generated tamoxifen-inducible mice with conditional inactivation of HDAC4 in Pax7+ cells (HDAC4 KO mice). We found that the proliferation and differentiation of HDAC4 KO satellite cells were compromised, although similar amounts of satellite cells were found in mice. Moreover, we found that the inhibition of HDAC4 in satellite cells was sufficient to block the differentiation process. By RNA-sequencing analysis we identified P21 and Sharp1 as HDAC4 target genes. Reducing the expression of these target genes in HDAC4 KO satellite cells, we also defined the molecular pathways regulated by HDAC4 in the epigenetic control of satellite cell expansion and fusion.

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Citations

Apr 5, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Cory M DunganCharlotte A Peterson
Jun 21, 2020·The FEBS Journal·Erica HurtadoMònica Suelves
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Datasets Mentioned

BETA
GSE106485

Methods Mentioned

BETA
acetylation
transgenic
fluorescence-activated cell sorting
PCR
FACS
histone acetylation
RNA-seq
enzymatic dissociation
transfection

Software Mentioned

Illumina
Image J
Image Lab
TopHat
Axiovision
Illumina cBot
CASAVA
Cuffdiff
ERNE

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