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MIM.604167 16q22.1

Sunday 19 March 2006

Transcriptional insulators are DNA elements that set boundaries on the actions of enhancer and silencer elements and thereby organize the eukaryotic genome into regulatory domains.

All vertebrate insulators appear to use the versatile CTCF protein. CTCF uses various combinations of its 11 zinc fingers to recognize a variety of unrelated DNA sequences. Once bound to DNA, CTCF can function as a transcriptional insulator, repressor, or activator, depending on the context of the binding site.

In normal cells, insulator proteins such as the transcription factor CTCF establish chromatin boundaries, and CTCF is involved in the regulation of imprinting, where it is required to protect against de novo methylation.

Intriguingly, methylation of the CTCF recognition sequence abolishes CTCF binding, indicating that specific DNA methylations may have long-range consequences.

CCCTC-binding factor (CTCF) is a chromatin insulator protein. It may play a central role in mediating long-range chromatin interactions, directing DNA segments into transcription factories and/or facilitating interactions with other DNA regions.

Several models that describe possible mechanisms for multiple functions of CTCF in establishment and maintenance of epigenetic programs are now emerging.

Epigenetics plays an important role in normal development and disease including cancer. CTCF involvement in multiple aspects of epigenetic regulation, including regulation of genomic imprinting and X-chromosome inactivation, has been well established.

More recently, CTCF was found to play a role in regulation of noncoding transcription and establishing local chromatin structure at the repetitive elements in mammalian genomes, suggesting a new epigenetic basis for several repeat-associated genetic disorders.


Emerging evidence also points to the role of CTCF deregulation in the epigenetic imbalance in cancer. These studies provide some of the important missing links in our understanding of epigenetic control of both development and cancer.

See also

- genomic imprinting
- DNA hypermethylation


- Ohlsson R, Renkawitz R, Lobanenkov V. CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease. Trends Genet. 2001 Sep;17(9):520-7. PMID: 11525835