Androgen receptor determines skeletal muscle sexual dimorphism
Sakai, H.; Yanagihara, Y.; Tanaka, K.; Tabuchi, A.; Iwamoto, H.; Horita, Y.; Otowa, S.; Kinoshita, T.; Watamori, K.; Hino, K.; Takao, M.; Maire, P.; Tajbakhsh, S.; Kosako, H.; Sawasaki, T.; Yamada, T.; Kano, Y.; Harada, A.; Ohkawa, Y.; Imai, Y.
Show abstract
The molecular and functional bases of sexual dimorphism in skeletal muscle remain poorly understood. The androgen receptor (AR) is a major regulator of sex-biased gene expression in muscle, but its genomic targets and associated coregulators in vivo are incompletely defined. Using ChIL-seq and an AirID-AR knock-in mouse, we mapped AR-bound genes and AR-associated proteins in skeletal muscle and identified histone deacetylase-linked corepressors. We further identified myosin binding protein H (Mybph) as a female-biased AR-repressed gene conserved in mouse and human muscle. Mybph loss disrupted sarcomeric organization and selectively delayed postinjury force recovery in female mice. These findings define an in vivo AR regulatory network and identify AR-dependent Mybph repression as a potential mechanism contributing to skeletal muscle sexual dimorphism.
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