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PMID:12270142

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Citation

Yousfi, M, Lasmoles, F and Marie, PJ (2002) TWIST inactivation reduces CBFA1/RUNX2 expression and DNA binding to the osteocalcin promoter in osteoblasts. Biochem. Biophys. Res. Commun. 297:641-4

Abstract

The Saethre-Chotzen (SC) syndrome is characterized by increased osteogenesis and premature fusion of cranial sutures, resulting from mutations in TWIST, a basic helix-loop-helix transcription factor. The molecular target genes for Twist in osteoblasts are however unknown. We report here that TWIST haploinsufficiency in mutant osteoblasts reduces mRNA and protein levels for CBFA1/RUNX2, a specific osteoblast transcription factor, during both osteoblast cell growth and in vitro osteogenesis. Moreover, this is associated with altered expression of major osteoblast-specific genes. Electrophoretic mobility shift assay (EMSA) showed reduced-binding ability of Cbfa1 to its target OSE2 element in the osteocalcin promoter in mutant osteoblasts. By contrast, TWIST inactivation does not hamper Cbfa1 binding on a similar upstream element present in the alpha1(I) collagen promoter in mutant osteoblasts. This provides the first evidence that TWIST inactivation alters CBFA1/RUNX2 expression and Cbfa1 binding ability to the osteocalcin promoter, indicating that CBFA1/RUNX2 is a target gene for TWIST in human osteoblasts.

Links

PubMed

Keywords

Acrocephalosyndactylia/genetics; Amino Acid Substitution; Base Sequence; Core Binding Factor Alpha 1 Subunit; DNA Primers; DNA-Binding Proteins/genetics; Gene Expression Regulation/physiology; Helix-Loop-Helix Motifs; Humans; Infant; Neoplasm Proteins; Nuclear Proteins; Osteoblasts/metabolism; Osteocalcin/genetics; Osteogenesis; Polymerase Chain Reaction; Promoter Regions, Genetic; Skull/abnormalities; Transcription Factors/genetics; Twist Transcription Factor

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:TWST1

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TWST1

involved_in

GO:2000679: positive regulation of transcription regulatory region DNA binding

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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