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PMID:16751105
| Citation |
Dobreva, G, Chahrour, M, Dautzenberg, M, Chirivella, L, Kanzler, B, Fariñas, I, Karsenty, G and Grosschedl, R (2006) SATB2 is a multifunctional determinant of craniofacial patterning and osteoblast differentiation. Cell 125:971-86 |
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| Abstract |
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. |
| Links |
PubMed Online version:10.1016/j.cell.2006.05.012 |
| Keywords |
Activating Transcription Factor 4/genetics; Animals; Body Patterning/genetics; Branchial Region/abnormalities; Branchial Region/cytology; Branchial Region/metabolism; Cell Differentiation/genetics; Core Binding Factor Alpha 1 Subunit/genetics; Craniofacial Abnormalities/genetics; Craniofacial Abnormalities/metabolism; Craniofacial Abnormalities/physiopathology; Facial Bones/abnormalities; Facial Bones/metabolism; Gene Expression Regulation, Developmental/genetics; Genes, Homeobox/genetics; Homeodomain Proteins/genetics; Matrix Attachment Region Binding Proteins/genetics; Mice; Mice, Knockout; Mutation/genetics; Osteoblasts/cytology; Osteoblasts/metabolism; Osteogenesis/genetics; Repressor Proteins/genetics; Skull/abnormalities; Transcription Factors/genetics |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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