Reference : Runx2-and histone deacetylase 3-mediated repression is relieved in differentiating human...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/1529
Runx2-and histone deacetylase 3-mediated repression is relieved in differentiating human osteoblast cells to allow high bone sialoprotein expression
English
Lamour, Virginie mailto [Université de Liège - ULg > > Centre facultaire de rech. en cancérologie expérimentale >]
Detry, Cédric mailto [Université de Liège - ULg > Centre facultaire de rech. en cancérologie expérimentale > > > >]
Sanchez, Christelle mailto [Université de Liège - ULg > Département des sciences de la motricité > Unité de recherche sur l'os et le cartillage (U.R.O.C.) >]
Henrotin, Yves mailto [Université de Liège - ULg > Département des sciences de la motricité > Unité de recherche sur l'os et le cartillage (U.R.O.C.) - Didactique des sciences de la santé - Pathologie générale et physiopathologie >]
Castronovo, Vincenzo mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire >]
Bellahcene, Akeila mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Labo de recherche sur les métastases >]
14-Dec-2007
Journal of Biological Chemistry
Amer Soc Biochemistry Molecular Biology Inc
282
50
36240-36249
Yes (verified by ORBi)
International
0021-9258
Bethesda
[en] BSP ; osteoblasts
[en] Bone sialoprotein (BSP) is a bone matrix glycoprotein whose expression coincides with terminal osteoblastic differentiation and the onset of mineralization. In this study we show that BSP expression is considerably increased in confluent Saos-2 human osteosarcoma cells and in differentiating normal human osteoblasts, concomitantly with the decrease of Runx2, a key transcription factor controlling bone formation. Therefore, we investigated the role of Runx2 in the regulation of BSP expression in Saos-2 cells. Using a mobility shift assay, we demonstrated that Runx2 binds to the BSP promoter only in preconfluent cells. Histone deacetylase 3 (HDAC3) has been recently shown to act as a Runx2 co-repressor. Chromatin immunoprecipitation assays demonstrated that both Runx2 and HDAC3 are detectable at the BSP promoter in preconfluent Saos-2 cells but not when they are confluent and overexpress BSP. Consistently, nuclear Runx2 protein level is down-regulated, whereas Saos-2 cells became increasingly confluent. Finally, the suppression of HDAC3, Runx2, or both by RNA interference induced the expression of BSP at both mRNA and protein levels in Saos-2 cells. Our data demonstrate that Runx2 and HDAC3 repress BSP gene expression and that this repression is suspended upon osteoblastic cell differentiation. Both the nuclear disappearance of Runx2 and the non-recruitment of HDAC3 represent new means to relieve Runx2-mediated suppression of BSP expression, thus allowing the acquisition of a fully differentiated and mineralization-competent phenotype by osteoblast cells.
http://hdl.handle.net/2268/1529
10.1074/jbc.M705833200

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