TY - JOUR
T1 - A Systems Approach Reveals that the Myogenesis Genome Network Is Regulated by the Transcriptional Repressor RP58
AU - Yokoyama, Shigetoshi
AU - Ito, Yoshiaki
AU - Ueno-Kudoh, Hiroe
AU - Shimizu, Hirohito
AU - Uchibe, Kenta
AU - Albini, Sonia
AU - Mitsuoka, Kazuhiko
AU - Miyaki, Shigeru
AU - Kiso, Minako
AU - Nagai, Akane
AU - Hikata, Tomohiro
AU - Osada, Tadahiro
AU - Fukuda, Noritsugu
AU - Yamashita, Satoshi
AU - Harada, Daisuke
AU - Mezzano, Valeria
AU - Kasai, Masataka
AU - Puri, Pier Lorenzo
AU - Hayashizaki, Yoshihide
AU - Okado, Haruo
AU - Hashimoto, Megumi
AU - Asahara, Hiroshi
PY - 2009/12/15
Y1 - 2009/12/15
N2 - 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.
AB - 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.
KW - DEVBIO
UR - http://www.scopus.com/inward/record.url?scp=71649095998&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=71649095998&partnerID=8YFLogxK
U2 - 10.1016/j.devcel.2009.10.011
DO - 10.1016/j.devcel.2009.10.011
M3 - Article
C2 - 20059953
AN - SCOPUS:71649095998
VL - 17
SP - 836
EP - 848
JO - Developmental Cell
JF - Developmental Cell
SN - 1534-5807
IS - 6
ER -