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Transcriptional repressor CTCF also known as 11-zinc finger protein or CCCTC-binding factor is a transcription factor that in humans is encoded by the CTCF gene. [ 5 ] [ 6 ] CTCF is involved in many cellular processes, including transcriptional regulation , insulator activity, V(D)J recombination [ 7 ] and regulation of chromatin architecture.
CTCF protein is known to favourably bind to unmethylated sites, so it follows that methylation of CpG islands is a point of epigenetic regulation. [2] An example of this is seen in the Igf2-H19 imprinted locus where methylation of the paternal imprinted control region (ICR) prevents CTCF from binding. [ 13 ]
CTCF molecules can form homodimers on DNA, which can be co-bound by cohesin; this chromatin loop structure helps constrain the ability of enhancers within the loop to target genes outside the loop. Loops with CTCF and cohesin at the start and end of the loop that restrict enhancer-gene targeting are "insulated neighborhoods."
Moreover, CTCF and cohesin play important roles in determining TADs and enhancer-promoter interactions. The result shows that the orientation of CTCF binding motifs in an enhancer-promoter loop should be facing to each other in order for the enhancer to find its correct target.
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This process continues until the extruding complex is released or encounters a barrier. In vertebrates, one well-studied factor that limits loop extrusion by cohesin is the CCCTC-binding factor (CTCF). CTCF directly interacts with cohesin, stabilizing it on chromatin and anchoring loop boundaries.