DNA-dependent formation of transcription factor pairs alters their binding specificity

摘要: Gene expression is regulated by transcription factors (TFs), proteins that recognize short DNA sequence motifs. Such sequences are very common in the human genome, and an important determinant of specificity gene cooperative binding multiple TFs to closely located However, interactions between DNA-bound have not been systematically characterized. To identify TF pairs bind cooperatively DNA, characterize their spacing orientation preferences, we performed consecutive affinity-purification systematic evolution ligands exponential enrichment (CAP-SELEX) analysis 9,400 TF-TF-DNA interactions. This revealed 315 TF-TF recognizing 618 heterodimeric motifs, most which previously described. The observed cooperativity occurred promiscuously from diverse structural families. Structural pairs, including a novel crystal structure MEIS1 DLX3 bound identified recognition site, were predominantly mediated DNA. Most pair sites involved large overlap individual resulted composite markedly different TF's Together, our results indicate molecule commonly plays active role define regulatory lexicon.