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

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

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)836-848
Number of pages13
JournalDevelopmental Cell
Volume17
Issue number6
DOIs
Publication statusPublished - Dec 15 2009
Externally publishedYes

Keywords

  • DEVBIO

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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    Yokoyama, S., Ito, Y., Ueno-Kudoh, H., Shimizu, H., Uchibe, K., Albini, S., Mitsuoka, K., Miyaki, S., Kiso, M., Nagai, A., Hikata, T., Osada, T., Fukuda, N., Yamashita, S., Harada, D., Mezzano, V., Kasai, M., Puri, P. L., Hayashizaki, Y., ... Asahara, H. (2009). A Systems Approach Reveals that the Myogenesis Genome Network Is Regulated by the Transcriptional Repressor RP58. Developmental Cell, 17(6), 836-848. https://doi.org/10.1016/j.devcel.2009.10.011