Genome wide identification of CTCF site disruption resulting in aberrant enhancer: promoter interactions as a recurrent mechanism of human disease

Study code

Lead researcher
Dr Christopher Cummings

Study type
Data only

Institution or company
University of Nebraska Medical Center, Omaha, USA

Researcher type

Speciality area
Genomics and Rare Diseases, Neurological Disorders

Recruitment Site
N/A (data only)


Organization of the genome in three-dimensional space is an emerging property of DNA with important roles in gene expression and cell differentiation. A major contributor to this organisation is the production of what have been termed CTCF loops. These are generated through a process where cohesion extrudes DNA into a loop until reaching a CTCF binding site, which thereby form the borders of these DNA loops. A functional consequence of loop generation is that enhancers and promoters located at long distances apart on the genome may be brought into close proximity inside of a loop and interact, thereby influencing gene transcription. Alternatively, promotors and enhancers on opposite sides of a CTCF boundary site are physically restricted from close interaction, and CTCF therefore acts as an important ‘insulator’ against aberrant promoter:enhancer interactions. Disruption of CTCF binding sites, therefore has the potential to interrupt the usual interplay between promoters and enhancers, and incidents of this in human disease are beginning to be discovered

We hypothesize that unbiased screening for CTCF binding site disruption genome-wide will identify additional examples of this novel mechanism of disease pathogenesis. Identification of CTCF site disruption important in human disease could identify novel genetic syndromes, could provide diagnoses for patients currently lacking one, and would be an important first step toward eventual treatment of their disease.