Prdm5 regulates collagen gene transcription by association with RNA polymerase II in developing bone

Giorgio Giacomo Galli, Kristian Honnens de Lichtenberg, Matteo Carrara, Wolfgang Hans, Manuela Wuelling, Bettina Mentz, Hinke Arnolda Multhaupt, Cathrine Kolster Fog, Klaus Thorleif Jensen, Juri Rappsilber, Andrea Vortkamp, Les Coulton, Helmut Fuchs, Valérie Gailus-Durner, Martin Hrabě de Angelis, Raffaele Adolfo Calogero, John Robert Couchman, Anders Henrik Lund

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere1002711
JournalPLoS Genetics
Volume8
Issue number5
DOIs
StatePublished - May 2012
Externally publishedYes

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