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Prdm5 regulates collagen gene transcription by association with RNA polymerase II in developing bone.
PLoS Genet. 8:e1002711 (2012)
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter BRITTLE CORNEA SYNDROME; TUMOR-SUPPRESSOR PRDM5; TARGETED DISRUPTION; GASTRIC-CANCER; 1ST INTRON; EXPRESSION; FAMILY; FIBRILLOGENESIS; CONTAINS; PATHWAY
ISSN (print) / ISBN 1553-7390
e-ISSN 1553-7404
Zeitschrift PLoS Genetics
Quellenangaben Band: 8, Heft: 5, Seiten: , Artikelnummer: e1002711 Supplement: ,
Verlag Public Library of Science (PLoS)
Begutachtungsstatus peer-reviewed