A Systems Approach Reveals that the Myogenesis Genome Network Is Regulated by the Transcriptional Repressor RP58

作者：Yokoyama Shigetoshi; Ito Yoshiaki; Ueno Kudoh Hiroe; Shimizu Hirohito; Uchibe Kenta; Albini Sonia; Mitsuoka Kazuhiko; Miyaki Shigeru; Kiso Minako; Nagai Akane; Hikata Tomohiro; Osada Tadahiro; Fukuda Noritsugu; Yamashita Satoshi; Harada Daisuke; Mezzano Valeria; Kasai Masataka; Puri Pier Lorenzo; Hayashizaki Yoshihide; Okado Haruo; Hashimoto Megumi; Asahara Hiroshi^*

来源：Developmental Cell, 2009, 17(6): 836-848.

DOI：10.1016/j.devcel.2009.10.011

We created a whole-mount in situ hybridization (WISH) database, termed EMBRYS, containing expression data of 1520 transcription factors and cofactors expressed in E9.5, E10.5, and E11.5 mouse embryos-a highly dynamic stage of skeletal myogenesis. This approach implicated 43 genes in regulation of embryonic myogenesis, including a transcriptional repressor, the zinc-finger protein RP58 (also known as Zfp238). Knockout and knockdown approaches confirmed an essential role for RP58 in skeletal myogenesis. Cell-based high-throughput transfection screening revealed that RP58 is a direct MyoD target. Microarray analysis identified two inhibitors of skeletal myogenesis, Id2 and Id3, as targets for RP58-mediated repression. Consistently, MyoD-dependent activation of the myogenic program is impaired in RP58 null fibroblasts and downregulation of Id2 and Id3 rescues MyoD's ability to promote myogenesis in these cells. Our combined, multi-system approach reveals a MyoD-activated regulatory loop relying on RP58-mediated repression of muscle regulatory factor (MRF) inhibitors.

• 出版日期2009-12-15
• 单位河北医科大学