Choice of binding sites for CTCFL compared to CTCF is driven by chromatin and by sequence preference

textabstractThe two paralogous zinc fingerfactors CTCFand CTCFL differ in expression such that CTCFis ubiquitously expressed, whereas CTCFL is found during spermatogenesis and in some cancer types in addition to other cell types. Both factors sharethe highly conserved DNA binding domainand are bound to DNA sequences with an identical consensus. In contrast, both factors differ substantially in the number of bound sites in the genome. Here, we addressed the molecular features for this binding specificity. In contrast to CTCFwe found CTCFL highly enriched at 'open' chromatin marked by H3K27 acetylation, H3K4 di- and trimethylation, H3K79 dimethylation and H3K9 acetylation plus the histone variantH2A.Z. CTCFL is enriched at transcriptional start sites and regions bound by transcription factors. Consequently, genes deregulated by CTCFL are highly cell specific. In addition to a chromatin-driven choice of binding sites, we determined nucleotide positions critical for DNA binding by CTCFL, but not by CTCF.