Prdm5 Regulates Collagen Gene Transcription by Association with RNA Polymerase II in Developing Bone

Research output: Contribution to journalJournal articleResearchpeer-review

  • Giorgio Giacomo Galli
  • Kristian Honnens de Lichtenberg
  • Matteo Carrara
  • Wolfgang Hans
  • Manuela Wuelling
  • Bettina Mentz
  • Multhaupt, Hinke Arnolda B V H
  • Cathrine Kolster Fog Tonnesen
  • Klaus Thorleif Jensen
  • Juri Rappsilber
  • Andrea Vortkamp
  • Les Coulton
  • Helmut Fuchs
  • Valérie Gailus-Durner
  • Martin Hrabe de Angelis
  • Raffaele Adolfo Calogero
  • Couchman, John Robert
  • Lund, Anders H.
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
JournalP L o S Genetics (Online)
Issue number5
Pages (from-to)e1002711
Publication statusPublished - 2012

ID: 38149836