CTCF sites are DNA sequences where the protein CTCF (CCCTC-binding factor) binds. These sites play a critical role in regulating gene expression by organizing the three-dimensional structure of the genome.
CTCF and its Function
CTCF is a highly conserved zinc finger protein that functions as a:
- Transcription factor: CTCF can activate or repress gene transcription.
- Insulator: CTCF prevents enhancers from activating promoters of genes located outside of a defined chromatin domain.
- Architectural protein: CTCF mediates long-range chromatin interactions and helps to form chromatin loops.
Role of CTCF Sites
CTCF sites are found throughout the genome and are often located at:
- Boundaries of topologically associating domains (TADs): TADs are self-interacting genomic regions that promote gene regulation within their boundaries, and CTCF helps define these boundaries, effectively separating active and inactive chromatin domains.
- Enhancer-like sequences: CTCF can bind to enhancer-like sequences and facilitate looping between these enhancers and gene promoters.
- Gene promoters: Similarly, CTCF can mediate looping between promoters, influencing gene expression.
How CTCF Sites Work
CTCF interacts with other proteins, such as cohesin, to form loops in the genome. These loops bring distant regions of the genome into close proximity, allowing enhancers to interact with promoters and regulate gene expression. The orientation of CTCF binding at these sites is also important for loop formation. Convergent orientations (pointing towards each other) are more likely to form loops.
Significance
CTCF sites are crucial for proper gene regulation and cellular function. Disruptions in CTCF binding or function have been implicated in various diseases, including cancer and developmental disorders.
