title: 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.
authors.affiliation: Department of Systems BioMedicine, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ito
authors.forename: Hiroe
authors.initials: H
authors.lastname: Ueno-Kudoh
authors.forename: Hirohito
authors.initials: H
authors.lastname: Shimizu
authors.forename: Kenta
authors.initials: K
authors.lastname: Uchibe
authors.forename: Sonia
authors.initials: S
authors.lastname: Albini
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Mitsuoka
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyaki
authors.forename: Minako
authors.initials: M
authors.lastname: Kiso
authors.forename: Akane
authors.initials: A
authors.lastname: Nagai
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Hikata
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Osada
authors.forename: Noritsugu
authors.initials: N
authors.lastname: Fukuda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamashita
authors.forename: Daisuke
authors.initials: D
authors.lastname: Harada
authors.forename: Valeria
authors.initials: V
authors.lastname: Mezzano
authors.forename: Masataka
authors.initials: M
authors.lastname: Kasai
authors.forename: Pier Lorenzo
authors.initials: PL
authors.lastname: Puri
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: Haruo
authors.initials: H
authors.lastname: Okado
authors.forename: Megumi
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asahara
mesh_terms: D000818:Animals; D055785:Gene Knockdown Techniques; D055786:Gene Knockout Techniques; D053263:Gene Regulatory Networks; D051797:Inhibitor of Differentiation Protein 2 / Q000378:metabolism; D051796:Inhibitor of Differentiation Proteins / Q000378:metabolism; D051379:Mice; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000196:embryology*; D018006:Myogenic Regulatory Factors / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*
chemical_list: C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D018006:Myogenic Regulatory Factors; D012097:Repressor Proteins; C520669:Zbtb18 protein, mouse; C067679:Idb3 protein, mouse