First Author | Galli GG | Year | 2012 |
Journal | PLoS Genet | Volume | 8 |
Issue | 5 | Pages | e1002711 |
PubMed ID | 22589746 | Mgi Jnum | J:185118 |
Mgi Id | MGI:5427503 | Doi | 10.1371/journal.pgen.1002711 |
Citation | Galli GG, et al. (2012) Prdm5 regulates collagen gene transcription by association with RNA polymerase II in developing bone. PLoS Genet 8(5):e1002711 |
abstractText | PRDM family members are transcriptional regulators involved in tissue specific differentiation. PRDM5 has been reported to predominantly repress transcription, but a characterization of its molecular functions in a relevant biological context is lacking. We demonstrate here that Prdm5 is highly expressed in developing bones; and, by genome-wide mapping of Prdm5 occupancy in pre-osteoblastic cells, we uncover a novel and unique role for Prdm5 in targeting all mouse collagen genes as well as several SLRP proteoglycan genes. In particular, we show that Prdm5 controls both Collagen I transcription and fibrillogenesis by binding inside the Col1a1 gene body and maintaining RNA polymerase II occupancy. In vivo, Prdm5 loss results in delayed ossification involving a pronounced impairment in the assembly of fibrillar collagens. Collectively, our results define a novel role for Prdm5 in sustaining the transcriptional program necessary to the proper assembly of osteoblastic extracellular matrix. |