A negatively-charged region within C-terminal domain maintains proper CTCF DNA binding (4C-Seq)

As an essential regulator of higher-order chromatin structures, CTCF is a highly conserved DNA binding protein with a central DNA-binding domain of 11 tandem zinc fingers, which are flanked by N- and C-terminal domains of intrinsically disordered regions. The N-terminal domain interacts with cohesin complex and the central ZF domains recognize a large range of diverse genomic sites. However, the function of C-terminal unstructured domain remains less understood. Here, we found that deletion of C-terminal fragment of 116 amino acid increases CTCF-DNA binding. By genetic dissection of this fragment, we uncovered a negatively-charged region responsible for repressing CTCF binding to DNA. Thus, the unstructured C-terminal domain play an important role in maintaining proper CTCF-DNA interactions. To investgate to foucntion of C-termnail of CTCF protein, we estabished several cell line of diifferent mutaion of CTCF and found a part of CTCF could repreess ite binding