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CTCF binds to the consensus sequence CCGCGNGGNGGCAG (in IUPAC notation). [22] [23] This sequence is defined by 11 zinc finger motifs in its structure. CTCF's binding is disrupted by CpG methylation of the DNA it binds to. [24] On the other hand, CTCF binding may set boundaries for the spreading of DNA methylation. [25]
Individuals with methylation aberrations at an imprinted CTCF-binding site near IGF2/H19 form aberrant Insulated Neighborhoods and develop Beckwith-Wiedemann syndrome (when both alleles have the paternal type of insulated neighborhood) or Silver-Russell syndrome (when both alleles have the maternal type of insulated neighborhood). [24]
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.
At this locus, CTCF functions as an insulator-binding protein forming a chromosomal boundary. [13] CTCF is present in both the chicken β-globin locus and human β-globin locus. Within cHS4 of the chicken β-globin locus, CTCF binds to a region (FII) that is responsible for enhancer blocking activity. [5]
The SMC can then either restart extruding or be unloaded by the additional binding of WAPL, which ensure proper recycling and turnover. Post-translational modifications also play a key role. Acetylation of cohesin by enzymes such as ESCO1 and ESCO2 stabilizes chromatin loops, particularly at CTCF-bound sites. Similarly, SUMOylation, mediated by ...
a database for CTCF binding sites and genome organization: database: website [7] Factorbook a Wiki-based database for transcription factor-binding data generated by the ENCODE consortium. database: website [8] hmChIP a database and web server for exploring publicly available human and mouse ChIP-seq and ChIP-chip data. database: website [9 ...
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]
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.