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Galli, G.G.* ; Honnens de Lichtenberg, K.* ; Carrara, M.* ; Hans, W. ; Wuelling, M.* ; Mentz, B.* ; Multhaupt, H.A.* ; Fog, C.K.* ; Jensen, K.T.* ; Rappsilber, J.* ; Vortkamp, A.* ; Coulton, L.* ; Fuchs, H.* ; Gailus-Durner, V. ; Hrabě de Angelis, M. ; Calogero, R.A.* ; Couchman, J.R.* ; Lund, A.H.*

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

PLoS Genet. 8:e1002711 (2012)

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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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