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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]
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.
TAD locations are defined by applying an algorithm to Hi-C data. For example, TADs are often called according to the so-called "directionality index". [5] The directionality index is calculated for individual 40kb bins, by collecting the reads that fall in the bin, and observing whether their paired reads map upstream or downstream of the bin (read pairs are required to span no more than 2Mb).
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The mechanism in which CTCF binds to these regions is currently unknown, but could include either a direct DNA-CTCF interaction or it could possibly be mediated by other proteins. In mammals (mice, humans, pigs), only the allele for insulin-like growth factor-2 ( IGF2 ) inherited from one's father is active; that inherited from the mother is ...