Aberrant homeodomain-DNA cooperative dimerization underlies distinct developmental defects in two dominant CRX retinopathy models.

ABSTRACT: Paired-class homeodomain transcription factors (HD TFs) play essential roles in vertebrate development, and their mutations are linked to human diseases. One unique feature of paired-class HD is cooperative dimerization on specific palindrome DNA sequences. Yet, the functional significance of HD cooperative dimerization in animal development and its dysregulation in diseases remain elusive. Using the retinal TF Cone-rod Homeobox (CRX) as a model, we have studied how blindness-causing mutations in the paired HD, p.E80A and p.K88N, alter CRX's cooperative dimerization, lead to gene misexpression and photoreceptor developmental deficits in dominant manners. CRX^E80A maintains binding at monomeric WT CRX motifs but is deficient in cooperative binding at dimeric motifs. CRX^E80A</

SUBMITTER: Zheng Y 

PROVIDER: S-EPMC10979960 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature