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Published on: March 31, 2019
CTCF directly binds G-quadruplex structures to regulate genome topology and gene expression
Daniela Samaniego-Castruita1, Isabella Han1, Roxroy C Morgan1
1Department of Cell and Developmental Biology, Northwestern University, Chicago, IL 60611.
DNA G-quadruplexes (G4s) are key DNA structures. This study reveals CCCTC-binding factor (CTCF) binds G4s, influencing genome organization, chromatin looping, and gene expression, establishing G4s
Area of Science:
- Genomics and molecular biology
- Structural biology
- Epigenetics
Background:
- DNA G-quadruplexes (G4s) are non-B-form DNA structures found in regulatory genomic regions.
- Their precise roles in genome function remain largely unknown.
- G4s are conserved across evolution, suggesting fundamental importance.
Purpose of the Study:
- To identify genomic regulators that bind G4s.
- To investigate the functional significance of G4 structures in genome regulation.
- To elucidate the interaction between G4s and the architectural protein CTCF.
Main Methods:
- Proteomics screening using diverse G4 topologies.
- Biochemical validation of CTCF-G4 interactions.
- Development of G4 mapping tools and genetic reconstitution experiments in mouse embryonic stem cells.
Main Results:
- CCCTC-binding factor (CTCF) identified as a strong G4 binder.
- A CTCF mutant with enhanced G4 affinity was characterized.
- A comprehensive catalog of genomic G4s associated with CTCF binding sites was generated.
- G4-linked chromatin loops exhibit increased strength and persistence.
Conclusions:
- CTCF directly binds DNA G-quadruplexes.
- G4 structures play a significant role in regulating CTCF binding, chromatin looping, and gene expression.
- G4s contribute to the stability and regulation of genome architecture.
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