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

Giorgio Giacomo Galli; Kristian Honnens de Lichtenberg; Matteo Carrara; Wolfgang Hans; Manuela Wuelling; Bettina Mentz; Hinke Arnolda Multhaupt; 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; John Robert Couchman; Anders Henrik Lund

doi:10.1371/journal.pgen.1002711

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

Giorgio Giacomo Galli, Kristian Honnens de Lichtenberg, Matteo Carrara, Wolfgang Hans, Manuela Wuelling, Bettina Mentz, Hinke Arnolda Multhaupt, 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, John Robert Couchman, Anders Henrik Lund

Nutritional Immunology

31 Citations (Scopus)

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.

Original language	English
Journal	P L o S Genetics (Online)
Volume	8
Issue number	5
Pages (from-to)	e1002711
ISSN	1553-7404
DOIs	https://doi.org/10.1371/journal.pgen.1002711
Publication status	Published - May 2012

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Galli, G. G., Honnens de Lichtenberg, K., Carrara, M., Hans, W., Wuelling, M., Mentz, B., Multhaupt, H. A., Tonnesen, C. K. F., Jensen, K. T., Rappsilber, J., Vortkamp, A., Coulton, L., Fuchs, H., Gailus-Durner, V., Hrabe de Angelis, M., Calogero, R. A., Couchman, J. R., & Lund, A. H. (2012). Prdm5 Regulates Collagen Gene Transcription by Association with RNA Polymerase II in Developing Bone. P L o S Genetics (Online), 8(5), e1002711. https://doi.org/10.1371/journal.pgen.1002711

Galli, GG, Honnens de Lichtenberg, K, Carrara, M, Hans, W, Wuelling, M, Mentz, B, Multhaupt, HA, Tonnesen, CKF, Jensen, KT, Rappsilber, J, Vortkamp, A, Coulton, L, Fuchs, H, Gailus-Durner, V, Hrabe de Angelis, M, Calogero, RA, Couchman, JR & Lund, AH 2012, 'Prdm5 Regulates Collagen Gene Transcription by Association with RNA Polymerase II in Developing Bone', P L o S Genetics (Online), vol. 8, no. 5, pp. e1002711. https://doi.org/10.1371/journal.pgen.1002711

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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.",

author = "Galli, {Giorgio Giacomo} and {Honnens de Lichtenberg}, Kristian and Matteo Carrara and Wolfgang Hans and Manuela Wuelling and Bettina Mentz and Multhaupt, {Hinke Arnolda} and Tonnesen, {Cathrine Kolster Fog} and Jensen, {Klaus Thorleif} and Juri Rappsilber and Andrea Vortkamp and Les Coulton and Helmut Fuchs and Val{\'e}rie Gailus-Durner and {Hrabe de Angelis}, Martin and Calogero, {Raffaele Adolfo} and Couchman, {John Robert} and Lund, {Anders Henrik}",

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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 - 2012/5

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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

SN - 1553-7404

VL - 8

SP - e1002711

JO - P L o S Genetics (Online)

JF - P L o S Genetics (Online)

IS - 5

ER -

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

Abstract

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