CTCF is a highly conserved multi-domain protein that primarily acts as a transcription factor. It is critical for organising overall genome structure and gene expression patterns (Hashimoto et al., 2017), functioning as an activator, repressor, or insulator protein. CTCF consists of a tandem of 11 Cys2-His2 (C2H2) zinc fingers (ZF). ZnF3-7 binds with DNA exclusively in the major groove, via a CTCF-binding motif. Shown in this model, each finger binds to three adjacent DNA base pairs of the core sequence (closely follows the consensus); ZF7 interacts with the 5′ sequence (CCA), ZF6 with the second triplet (GCA), ZF5 with the third triplet (GGG), ZF4 with the fourth triplet (GGC), and ZF3 with the 3′ sequence (GCT). This tour shows the structure of human CTCF (ZF2-7) in complex with DNA, detailing four specific examples of interactions that convey the versatile and methylation dependent binding of CTCF to DNA, which ultimately facilitates the multi-faceted functionality of CTCF.
10.1016/j.molcel.2017.05.004
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