Basic helix-loop-helix (bHLH) transcription factors have been implicated in cell lineage determination and differentiation. The protein encoded by this gene is a bHLH transcription factor and shares similarity with another bHLH transcription factor, Dermo1. The strongest expression of this mRNA is in placental tissue; in adults, mesodermally derived tissues express this mRNA preferentially. Mutations in this gene have been found in patients with Saethre-Chotzen syndrome. [provided by RefSeq, Jul 2008]

TWIST1: Acts as a transcriptional regulator. Inhibits myogenesis by sequestrating E proteins, inhibiting trans-activation by MEF2, and inhibiting DNA-binding by MYOD1 through physical interaction. This interaction probably involves the basic domains of both proteins. Also represses expression of proinflammatory cytokines such as TNFA and IL1B. Regulates cranial suture patterning and fusion. Activates transcription as a heterodimer with E proteins. Regulates gene expression differentially, depending on dimer composition. Homodimers induce expression of FGFR2 and POSTN while heterodimers repress FGFR2 and POSTN expression and induce THBS1 expression. Heterodimerization is also required for osteoblast differentiation. Efficient DNA binding requires dimerization with another bHLH protein. Homodimer or heterodimer with E proteins such as TCF3. ID1 binds preferentially to TCF3 but does not interact efficiently with TWIST1 so ID1 levels control the amount of TCF3 available to dimerize with TWIST1 and thus determine the type of dimer formed. Subset of mesodermal cells.

Protein type: Cell development/differentiation; Inhibitor; DNA-binding; Transcription regulation

Chromosomal Location of Human Ortholog: 7p21.2

Cellular Component: nucleus

Molecular Function: bHLH transcription factor binding; protein binding; protein domain specific binding; protein heterodimerization activity; protein homodimerization activity; transcription factor binding

Biological Process: embryonic cranial skeleton morphogenesis; embryonic digit morphogenesis; embryonic forelimb morphogenesis; embryonic hindlimb morphogenesis; in utero embryonic development; muscle development; negative regulation of apoptosis; negative regulation of DNA damage response, signal transduction by p53 class mediator; negative regulation of histone acetylation; negative regulation of histone phosphorylation; negative regulation of osteoblast differentiation; negative regulation of phosphoinositide 3-kinase cascade; negative regulation of skeletal muscle development; negative regulation of transcription factor activity; negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription, DNA-dependent; negative regulation of tumor necrosis factor production; neural tube closure; neuron migration; odontogenesis; ossification; osteoblast differentiation; outer ear morphogenesis; palate development; positive regulation of angiogenesis; positive regulation of epithelial cell proliferation; positive regulation of fatty acid beta-oxidation; positive regulation of transcription from RNA polymerase II promoter; positive regulation of tumor necrosis factor production; regulation of bone mineralization; rhythmic process; transcription, DNA-dependent

Disease: Craniosynostosis 1; Robinow-sorauf Syndrome; Saethre-chotzen Syndrome