Insights into interplay between rexinoid signaling and myogenic regulatory factor-associated chromatin state in myogenic differentiation

Autor: Ilya Ioshikhes, Katherine Dixon, Jihong Chen, Qiao Li, Munerah Hamed, Alexandre Blais, Saadia Khilji
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Nucleic Acids Research
ISSN: 1362-4962
0305-1048
Popis: While skeletal myogenesis is tightly coordinated by myogenic regulatory factors including MyoD and myogenin, chromatin modifications have emerged as vital mechanisms of myogenic regulation. We have previously established that bexarotene, a clinically approved agonist of retinoid X receptor (RXR), promotes the specification and differentiation of skeletal muscle lineage. Here, we examine the genome-wide impact of rexinoids on myogenic differentiation through integral RNA-seq and ChIP-seq analyses. We found that bexarotene promotes myoblast differentiation through the coordination of exit from the cell cycle and the activation of muscle-related genes. We uncovered a new mechanism of rexinoid action which is mediated by the nuclear receptor and largely reconciled through a direct regulation of MyoD gene expression. In addition, we determined a rexinoid-responsive residue-specific histone acetylation at a distinct chromatin state associated to MyoD and myogenin. Thus, we provide novel molecular insights into the interplay between RXR signaling and chromatin states pertinent to myogenic programs in early myoblast differentiation.
Databáze: OpenAIRE