Decoding the mechanisms of cooperative DNA binding by the Paired-like homeodomain family.

ABSTRACT: The 36 Paired-like homeodomain transcription factors are required for the development of many cell types, tissues, and organs as missense variants in 24 genes are associated with a variety of diseases and developmental disorders. How these factors identify distinct genomic targets using highly similar DNA binding domains is not fully understood. Here, we focus on determining how the Paired-like homeodomain factors gain DNA binding specificity by cooperatively binding palindromic sites spaced three base pairs apart (P3 site). Through structural, biochemical, and bioinformatic approaches, we define 11 rules that describe homeodomain residues that are critical, permissive, and inhibitory to cooperativity on the P3 site. Applying these rules, we successfully altered the cooperative behavior of

SUBMITTER: Cain B 

PROVIDER: S-EPMC12636397 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature