Regulation of the osteoblast-specific transcription factor Osterix by NO66, a Jumonji family histone demethylase
Open Access
- 19 November 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 29 (1), 68-79
- https://doi.org/10.1038/emboj.2009.332
Abstract
Osterix (Osx) is an osteoblast‐specific transcription factor required for osteoblast differentiation and bone formation. Osx null mice develop a normal cartilage skeleton but fail to form bone and to express osteoblast‐specific marker genes. To better understand the control of transcriptional regulation by Osx, we identified Osx‐interacting proteins using proteomics approaches. Here, we report that a Jumonji C (JmjC)‐domain containing protein, called NO66, directly interacts with Osx and inhibits Osx‐mediated promoter activation. The knockdown of NO66 in preosteoblast cells triggered accelerated osteoblast differentiation and mineralization, and markedly stimulated the expression of Osx target genes. A JmjC‐dependent histone demethylase activity was exhibited by NO66, which was specific for both H3K4me and H3K36me in vitro and in vivo , and this activity was needed for the regulation of osteoblast‐specific promoters. During BMP‐2‐induced differentiation of preosteoblasts, decreased NO66 occupancy correlates with increased Osx occupancy at Osx‐target promoters. Our results indicate that interactions between NO66 and Osx regulate Osx‐target genes in osteoblasts by modulating histone methylation states.Keywords
This publication has 37 references indexed in Scilit:
- Msx2 Exerts Bone Anabolism via Canonical Wnt SignalingJournal of Biological Chemistry, 2008
- New Nomenclature for Chromatin-Modifying EnzymesCell, 2007
- The Histone H3 Lysine-27 Demethylase Jmjd3 Links Inflammation to Inhibition of Polycomb-Mediated Gene SilencingCell, 2007
- UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and developmentNature, 2007
- Jmjd2b antagonizes H3K9 trimethylation at pericentric heterochromatin in mammalian cellsGenes & Development, 2006
- Canonical Wnt/β-Catenin Signaling Prevents Osteoblasts from Differentiating into ChondrocytesDevelopmental Cell, 2005
- Dlx3 Transcriptional Regulation of Osteoblast Differentiation: Temporal Recruitment of Msx2, Dlx3, and Dlx5 Homeodomain Proteins to Chromatin of the Osteocalcin GeneMolecular and Cellular Biology, 2004
- NO66, a Highly Conserved Dual Location Protein in the Nucleolus and in a Special Type of Synchronously Replicating ChromatinMolecular Biology of the Cell, 2004
- Chondrogenic cell differentiation from membrane bone periostea.Brain Structure and Function, 1997
- Osf2/Cbfa1: A Transcriptional Activator of Osteoblast DifferentiationCell, 1997