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
N1 - Funding Information:
We thank H. Naito, T. Suzuki, D. Kozaki, H. Ishitobi, M. Horiuchi, K.Sakuma, J. Hasegawa, and all other Asahara lab members for help with construction of EMBRYS; M. Asada, T. Watanabe, and T. Yoshitaka for construction and assistance with HTS; G. Lindman for assistance with vector construction; Y. Kawakami and J.C. Belmonte for technical advice; Y. Takahashi and K. Yanagisawa for help with bioinformatics information and construction of the webpage; N. Hashimoto for help with setting up microarray instruments; A. Miwa for help with collecting RP58 mutant embryos; Y. Nabeshima for sharing Myog mutant mice; and T. Tanaka, S. Hiraoka, and G. Lindman for critical reading of the manuscript and discussion. Y. Ito and H. Asahara are associate scientists of Tokyo Medical & Dental University. This project was supported by Grants from the Genome Network Project (MEXT) and partially from SORST (JST), Grants from the Ministry of Health, Labour and Welfare, Grants-in Aid for Scientific Research (MEXT), and Grant ID 05-24 from the National Institute of Biomedical Innovation. P.L.P is an associate scientist of Telethon Dulbecco Institute and of Sanford Children's Health Center and was partially supported by AIRC and NIAMS (RO1AR052779).
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
SN - 1534-5807
VL - 17
SP - 836
EP - 848
JO - Developmental Cell
JF - Developmental Cell
IS - 6
ER -