The multidomain CCCTC-binding factor (CTCF) is encoded throughout the mammalian chromosomes (approximately 80000 sites). It contains a tandem array of 11 zinc finger (ZF) domains that can remodel the 3D structure of chromatin. Thus, the protein can modulate the structure of the genome, establishing patterns of gene expression in higher organisms such as Eukaryotes. The six zinc fingers (ZF2-7) interact with DNA exclusively in the major groove via base-specific contacts. 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). In the structure of ZF2-7 in complex with DNA, ZF2 continues to follow in the major groove, but the side chains within the DNA-interacting helix were too far away (> 4Å) to make base-specific hydrogen bonds. ZF2-ruby; ZF3-yellow;ZF4-cyan;ZF5-blue;ZF6-green;ZF7-magenta;DNA-ribbon. Residue numbering is according to the top strand of 15 bp CORE sequence. PDB: 5T0U
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