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Incorporation of histone H3.1 suppresses the lineage potential of skeletal muscle
Author(s) -
Akihito Harada,
Kazumitsu Maehara,
Yuko Sato,
Daijiro Konno,
Taro Tachibana,
Hiroshi Kimurâ,
Yasuyuki Ohkawa
Publication year - 2014
Publication title -
nucleic acids research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.008
H-Index - 537
eISSN - 1362-4954
pISSN - 0305-1048
DOI - 10.1093/nar/gku1346
Subject(s) - h3k4me3 , biology , histone h3 , myod , myogenesis , chromatin immunoprecipitation , histone , skeletal muscle , microbiology and biotechnology , chromatin , myogenin , genetics , myocyte , gene , promoter , gene expression , anatomy
Lineage potential is triggered by lineage-specific transcription factors in association with changes in the chromatin structure. Histone H3.3 variant is thought to play an important role in the regulation of lineage-specific genes. To elucidate the function of H3.3 in myogenic differentiation, we forced the expression of GFP-H3.1 to alter the balance between H3.1 and H3.3 in mouse C2C12 cells that could be differentiated into myotubes. GFP-H3.1 replaced H3.3 in the regulatory regions of skeletal muscle (SKM) genes and induced a decrease of H3K4 trimethylation (H3K4me3) and increase of H3K27 trimethylation (H3K27me3). Similar results were obtained by H3.3 knockdown. In contrast, MyoD-dependent H3.3 incorporation into SKM genes in fibroblasts induced an increase of H3K4me3 and H3K27me3. In mouse embryos, a bivalent modification of H3K4me3 and H3K27me3 was formed on H3.3-incorporated SKM genes before embryonic skeletal muscle differentiation. These results suggest that lineage potential is established through a selective incorporation of specific H3 variants that governs the balance of histone modifications.

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