[8] CCCTC-Binding factor or CTCF was initially discovered as a negative regulator of the chicken c-myc gene.

CTCF is thought to be a primary part of the activity of insulators, sequences that block the interaction between enhancers and promoters.

In each case, it is unknown if CTCF directly evokes the outcome or if it does so indirectly (in particular through its looping role).

The protein CTCF plays a heavy role in repressing the insulin-like growth factor 2 gene, by binding to the H-19 imprinting control region (ICR) along with differentially-methylated region-1 (DMR1) and MAR3.

[16] CTCF also occurs frequently at the boundaries of sections of DNA bound to the nuclear lamina.

[24] On the other hand, CTCF binding may set boundaries for the spreading of DNA methylation.

[29] CTCF's ability to bind to multiple sequences through the usage of various combinations of its zinc fingers earned it the status of a “multivalent protein”.

[33] Methylation loss at CTCF-binding site of some genes has been found to be related to human diseases, including male infertility.