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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)
Verlagsversion Volltext DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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