TBX22 missense mutations found in patients with X-linked cleft palate affect DNA binding, sumoylation, and transcriptional repression.

ABSTRACT: The T-box transcription factor TBX22 is essential for normal craniofacial development, as demonstrated by the finding of nonsense, frameshift, splice-site, or missense mutations in patients with X-linked cleft palate (CPX) and ankyloglossia. To better understand the function of TBX22, we studied 10 different naturally occurring missense mutations that are phenotypically equivalent to loss-of-function alleles. Since all missense mutations are located in the DNA-binding T-box domain, we first investigated the preferred recognition sequence for TBX22. Typical of T-box proteins, the resulting sequence is a palindrome based around near-perfect copies of AGGTGTGA. DNA-binding assays indicate that missense mutations at or near predicted contact points with the DNA backbone compromise stable DNA-p

SUBMITTER: Andreou AM 

PROVIDER: S-EPMC2227921 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature