Prdm5 Regulates Collagen Gene Transcription by Association with RNA Polymerase II in Developing Bone
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Prdm5 Regulates Collagen Gene Transcription by Association with RNA Polymerase II in Developing Bone. / Galli, Giorgio Giacomo; Honnens de Lichtenberg, Kristian; Carrara, Matteo; Hans, Wolfgang; Wuelling, Manuela; Mentz, Bettina; Multhaupt, Hinke Arnolda; Tonnesen, Cathrine Kolster Fog; Jensen, Klaus Thorleif; Rappsilber, Juri; Vortkamp, Andrea; Coulton, Les; Fuchs, Helmut; Gailus-Durner, Valérie; Hrabe de Angelis, Martin; Calogero, Raffaele Adolfo; Couchman, John Robert; Lund, Anders Henrik.
In: P L o S Genetics (Online), Vol. 8, No. 5, 2012, p. e1002711.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Prdm5 Regulates Collagen Gene Transcription by Association with RNA Polymerase II in Developing Bone
AU - Galli, Giorgio Giacomo
AU - Honnens de Lichtenberg, Kristian
AU - Carrara, Matteo
AU - Hans, Wolfgang
AU - Wuelling, Manuela
AU - Mentz, Bettina
AU - Multhaupt, Hinke Arnolda
AU - Tonnesen, Cathrine Kolster Fog
AU - Jensen, Klaus Thorleif
AU - Rappsilber, Juri
AU - Vortkamp, Andrea
AU - Coulton, Les
AU - Fuchs, Helmut
AU - Gailus-Durner, Valérie
AU - Hrabe de Angelis, Martin
AU - Calogero, Raffaele Adolfo
AU - Couchman, John Robert
AU - Lund, Anders Henrik
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pgen.1002711
DO - 10.1371/journal.pgen.1002711
M3 - Journal article
C2 - 22589746
VL - 8
SP - e1002711
JO - P L o S Genetics
JF - P L o S Genetics
SN - 1553-7390
IS - 5
ER -
ID: 38149836