TY - JOUR
T1 - SATB2 Is a Multifunctional Determinant of Craniofacial Patterning and Osteoblast Differentiation
AU - Dobreva, Gergana
AU - Chahrour, Maria
AU - Dautzenberg, Marcel
AU - Chirivella, Laura
AU - Kanzler, Benoit
AU - Fariñas, Isabel
AU - Karsenty, Gerard
AU - Grosschedl, Rudolf
N1 - Funding Information:
We thank Drs. A. Gründer, M. Kieslinger, W. Roth, A. Neubüser, N. Bobola, M. Feuring-Buske, and C. Bleul for discussions and advice. We are grateful to Drs. F. Rijli and E. Wagner for discussions and helpful suggestions. We thank Drs. T. Lufkin and T. Gridley for plasmids and Hoxa2 +/− mice, respectively. This work was supported by funds of the Max Planck Society and the DFG to R.G.I.F. is funded by the Spanish Ministerios de Educación y Ciencias y de Sanidad.
PY - 2006/6/2
Y1 - 2006/6/2
N2 - Vertebrate skeletogenesis involves two processes, skeletal patterning and osteoblast differentiation. Here, we show that Satb2, encoding a nuclear matrix protein, is expressed in branchial arches and in cells of the osteoblast lineage. Satb2-/- mice exhibit both craniofacial abnormalities that resemble those observed in humans carrying a translocation in SATB2 and defects in osteoblast differentiation and function. Multiple osteoblast-specific genes were identified as targets positively regulated by SATB2. In addition, SATB2 was found to repress the expression of several Hox genes including Hoxa2, an inhibitor of bone formation and regulator of branchial arch patterning. Molecular analysis revealed that SATB2 directly interacts with and enhances the activity of both Runx2 and ATF4, transcription factors that regulate osteoblast differentiation. This synergy was genetically confirmed by bone formation defects in Satb2/Runx2 and Satb2/Atf4 double heterozygous mice. Thus, SATB2 acts as a molecular node in a transcriptional network regulating skeletal development and osteoblast differentiation.
AB - Vertebrate skeletogenesis involves two processes, skeletal patterning and osteoblast differentiation. Here, we show that Satb2, encoding a nuclear matrix protein, is expressed in branchial arches and in cells of the osteoblast lineage. Satb2-/- mice exhibit both craniofacial abnormalities that resemble those observed in humans carrying a translocation in SATB2 and defects in osteoblast differentiation and function. Multiple osteoblast-specific genes were identified as targets positively regulated by SATB2. In addition, SATB2 was found to repress the expression of several Hox genes including Hoxa2, an inhibitor of bone formation and regulator of branchial arch patterning. Molecular analysis revealed that SATB2 directly interacts with and enhances the activity of both Runx2 and ATF4, transcription factors that regulate osteoblast differentiation. This synergy was genetically confirmed by bone formation defects in Satb2/Runx2 and Satb2/Atf4 double heterozygous mice. Thus, SATB2 acts as a molecular node in a transcriptional network regulating skeletal development and osteoblast differentiation.
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U2 - 10.1016/j.cell.2006.05.012
DO - 10.1016/j.cell.2006.05.012
M3 - Article
C2 - 16751105
AN - SCOPUS:33744536200
SN - 0092-8674
VL - 125
SP - 971
EP - 986
JO - Cell
JF - Cell
IS - 5
ER -