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Repression of the slow type I myosin gene in skeletal muscle correlates with enrichment of repressive histone modifications in its promoter region
Author(s) -
Pandorf Clay E,
Haddad Fadia,
Qin Anqi X,
Baldwin Kenneth M
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1105.11
Subject(s) - chromatin immunoprecipitation , microbiology and biotechnology , myosin , histone h3 , histone , psychological repression , gene , biology , chromatin , gene expression , promoter , genetics
Unloading of slow fatigue resistant skeletal muscle results in a fast and more fatigable phenotype. This is manifest in transcriptional downregulation of the types I and IIa myosin heavy chain (MHC) genes, which is further augmented by thyroid hormone (T3). Regulation of gene transcription is ultimately governed by signals in the histones around which the genes are wrapped; we examined the role of repressive histone modifications at the MHC genes. Rats were hindlimb unloaded by tail suspension (HS) for 7d, or given T3 with HS (HS+T3), or untreated (CON). Chromatin immunoprecipitation (ChIP) was used to assess gene enrichment of histone H3K9 di‐ and tri‐ methylation (me2 and me3) and H3K27me2 in the soleus. The percent of slow type I MHC mRNA in CON, HS and HS+T3 was 77%, 32%, and 5% respectively. It was 17%, 1%, and <1% for the IIa MHC, respectively. The repression of both type I and IIa MHC genes was accompanied by significant (p<0.05) gene enrichment of H3K9me2 and H3K27me2 in HS+T3 as compared to CON. There was a significant (p<0.01) inverse correlation (r=−0.75) between type I MHC mRNA levels and H3K9me2 across groups. In conclusion, dynamic and marked repression of the type I and IIa MHC genes with HS+T3, but not with HS alone, results in gene enrichment of dimethylation at H3K9 and K27, which initiates a conversion of the chromatin state to a restrictive transcriptional environment. Supported by NIH AR30346 & NSBRI NCC 9–58.