DACH1
Description
The DACH1 (dachshund family transcription factor 1) is a protein-coding gene located on chromosome 13.
Dachshund homolog 1, also known as DACH1, is a protein encoded by the DACH1 gene in humans. DACH1 interacts with Ubc9, Smad4, and NCoR. It is a chromatin-associated protein that works with other DNA-binding transcription factors to control gene expression, mRNA translation, coactivator binding, and cell fate determination during development. The DACH1 gene has 12 exons and encodes a 760 amino acid protein with an observed molecular weight of 52 kDa. It is located on human chromosome 13 (13q22). Multiple transcript variants encoding different isoforms have been found for this gene, including four alternatively spliced transcripts. DACH1 mRNA is detected in various human tissues, including kidney and heart. Dach1 resides in both nuclear and cytoplasmic pools and is considered a cell fate determination factor. Its DACHbox-N domain has a predicted helix–turn–helix family structure and contains a conserved domain similar to the pro-oncogenes ski/sno oncogenes. The X-ray crystal structure of the human DACH1 Box-N reveals an α/β structure similar to that found in the winged helix/forkhead subgroup of DNA binding proteins.
DACH1 is a transcription factor that plays a crucial role in regulating organ development. It interacts with other transcription factors like SIX1, SIX6, and potentially SIX5, influencing their activity. Notably, DACH1 switches from corepressing SIX1-mediated cell proliferation in myoblasts to coactivating it by recruiting EYA3 to the SIX1-DACH1 complex. DACH1's association with CREBBP suggests involvement in transcriptional activation. As a corepressor of SIX6, DACH1 regulates proliferation by directly repressing cyclin-dependent kinase inhibitors, including the p27Kip1 promoter. Furthermore, DACH1 inhibits TGF-beta signaling by interacting with SMAD4 and NCOR1. It binds to chromatin DNA through its DACHbox-N domain.
DACH1 is also known as DACH.
