title: Prdm5 regulates collagen gene transcription by association with RNA polymerase II in developing bone.
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.
authors.affiliation: Biotech Research and Innovation Centre and Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Giorgio Giacomo
authors.initials: GG
authors.lastname: Galli
authors.forename: Kristian
authors.initials: K
authors.lastname: Honnens de Lichtenberg
authors.forename: Matteo
authors.initials: M
authors.lastname: Carrara
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hans
authors.forename: Manuela
authors.initials: M
authors.lastname: Wuelling
authors.forename: Bettina
authors.initials: B
authors.lastname: Mentz
authors.forename: Hinke Arnolda
authors.initials: HA
authors.lastname: Multhaupt
authors.forename: Cathrine Kolster
authors.initials: CK
authors.lastname: Fog
authors.forename: Klaus Thorleif
authors.initials: KT
authors.lastname: Jensen
authors.forename: Juri
authors.initials: J
authors.lastname: Rappsilber
authors.forename: Andrea
authors.initials: A
authors.lastname: Vortkamp
authors.forename: Les
authors.initials: L
authors.lastname: Coulton
authors.forename: Helmut
authors.initials: H
authors.lastname: Fuchs
authors.forename: Valérie
authors.initials: V
authors.lastname: Gailus-Durner
authors.forename: Martin
authors.initials: M
authors.lastname: Hrabě de Angelis
authors.forename: Raffaele Adolfo
authors.initials: RA
authors.lastname: Calogero
authors.forename: John Robert
authors.initials: JR
authors.lastname: Couchman
authors.forename: Anders Henrik
authors.initials: AH
authors.lastname: Lund
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001846:Bone Development / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D058575:Decorin / Q000235:genetics / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D024022:Fibrillar Collagens; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D051379:Mice; D009928:Organ Specificity; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D004268:DNA-Binding Proteins; D058575:Decorin; D024022:Fibrillar Collagens; C575119:PRDM5 protein, mouse; D011509:Proteoglycans; D014157:Transcription Factors; D012319:RNA Polymerase II