| First Author | Yokoyama S | Year | 2009 |
| Journal | Dev Cell | Volume | 17 |
| Issue | 6 | Pages | 836-48 |
| PubMed ID | 20059953 | Mgi Jnum | J:156017 |
| Mgi Id | MGI:4418579 | Doi | 10.1016/j.devcel.2009.10.011 |
| Citation | Yokoyama S, et al. (2009) A systems approach reveals that the myogenesis genome network is regulated by the transcriptional repressor RP58. Dev Cell 17(6):836-48 |
| abstractText | 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. |
