Loci-specific histone acetylation profiles associated with transcriptional coactivator p300 during early myoblast differentiation.

ABSTRACT

Molecular regulation of stem cell differentiation is exerted through both genetic and epigenetic determinants over distal regulatory or enhancer regions. Understanding the mechanistic action of active or poised enhancers is therefore imperative for control of stem cell differentiation. Based on the genome-wide co-occurrence of different epigenetic marks in committed proliferating myoblasts, we have previously generated a 14-state chromatin state model to profile rexinoid-responsive histone acetylation in early myoblast differentiation. Here, we delineate the functional mode of transcription regulators during early myogenic differentiation using genome-wide chromatin state association. We define a role of transcriptional coactivator p300, when recruited by muscle master regulator MyoD, in the establishment and regulation of myogenic loci at the onset of myoblast differentiation. In addition, we reveal an enrichment of loci-specific histone acetylation at p300 associated active or poised enhancers, particularly when enlisted by MyoD. We provide novel molecular insights into the regulation of myogenic enhancers by p300 in concert with MyoD. Our studies present a valuable aptitude for driving condition-specific chromatin state or enhancers pharmacologically to treat muscle-related diseases and for the identification of additional myogenic targets and molecular interactions for therapeutic development. ABBREVIATIONS MRF Muscle regulatory factor; HAT Histone acetyltransferase; CBP CREB-binding protein; ES Embryonic stem; ATCC American type culture collection; DM Differentiation medium; DMEM Dulbecco's Modified Eagle Medium; GM Growth medium; GO Gene ontology; GREAT Genomic regions enrichment of annotations tool; FPKM Fragments per kilobase of transcript per million; GEO Gene expression omnibus; MACS Model-based analysis for ChIP-seq.