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A systems approach reveals that the myogenesis genome network is regulated by the transcriptional repressor RP58.

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.

SUBMITTER: Yokoyama S

PROVIDER: S-EPMC3110151 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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A systems approach reveals that the myogenesis genome network is regulated by the transcriptional repressor RP58.

Yokoyama Shigetoshi S Ito Yoshiaki Y Ueno-Kudoh Hiroe H Shimizu Hirohito H Uchibe Kenta K Albini Sonia S Mitsuoka Kazuhiko K Miyaki Shigeru S Kiso Minako M Nagai Akane A Hikata Tomohiro T Osada Tadahiro T Fukuda Noritsugu N Yamashita Satoshi S Harada Daisuke D Mezzano Valeria V Kasai Masataka M Puri Pier Lorenzo PL Hayashizaki Yoshihide Y Okado Haruo H Hashimoto Megumi M Asahara Hiroshi H

Developmental cell 20091201 6

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 myog ...[more]

PMID: 20059953

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Dataset Information

A systems approach reveals that the myogenesis genome network is regulated by the transcriptional repressor RP58.

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A systems approach reveals that the myogenesis genome network is regulated by the transcriptional repressor RP58.

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