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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 ]
CCCTC-binding factor , an 11-zinc finger factor involved in gene regulation, utilizes different zinc fingers to bind varying DNA target sites. CTCF forms methylation-sensitive insulators that regulate X-chromosome inactivation .
Insulated neighborhoods are defined as chromosome loops that are formed by CTCF homodimers, co-bound with cohesin, and containing at least one gene. [13] [14] The CTCF/cohesin-bound regions delimiting an insulated neighborhood are called "anchors."
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. [51]
A number of proteins are known to be associated with TAD formation including the protein CTCF and the protein complex cohesin. [1] It is also unknown what components are required at TAD boundaries; however, in mammalian cells, it has been shown that these boundary regions have comparatively high levels of CTCF binding.
Due to the ability of Hi-C to depict dynamic interactions in differentiation-related TADs, the researchers discovered increases in the number of DHS sites, CTCF binding ability, active histone modifications, and target gene expressions within these TADs of interest, and found significant participation of major pluripotency factors such as OCT4 ...
Other genes often used clusters of weaker consensus motifs, possibly to achieve a similar occupancy. Binding motifs of CTCF employed four "modules". Half of the bound CTCF sites used modules 1 and 2, while the rest used some combination of the four. It is believed that CTCF uses its zinc fingers to recognize different combinations of these ...