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HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries
Published on: March 31, 2019
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Multi-feature clustering of CTCF binding creates robustness for loop extrusion blocking and Topologically Associating
Li-Hsin Chang1,2, Sourav Ghosh1,3, Andrea Papale4
1Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198, Gif-sur-Yvette, France.
Nature Communications
|September 12, 2023
Summary
Topologically Associating Domains (TADs) are insulated genomic regions. CTCF binding sites clustered at TAD boundaries block genome-wide loop extrusion, creating stepwise insulation.
Area of Science:
- Genomics
- Molecular Biology
- Epigenetics
Background:
- Topologically Associating Domains (TADs) define regulatory units in vertebrate genomes.
- TADs are formed by cohesin-mediated loop extrusion.
- Many TAD boundaries feature clustered CTCF insulator protein binding sites.
Purpose of the Study:
- To investigate how clustered CTCF binding sites contribute to blocking loop extrusion.
- To understand the mechanism of insulation between TADs.
Main Methods:
- Analysis of CTCF binding site features at TAD boundaries.
- Multi-contact Nano-C analysis in cells with normal and perturbed CTCF binding.
Main Results:
- Strong TAD boundaries show enrichment of closely spaced, strongly bound CTCF sites with DNA-binding motifs.
- Individual CTCF binding sites partially block loop extrusion.
- Clustered CTCF binding sites create stepwise insulation between TADs.
Conclusions:
- Clustered CTCF binding sites are crucial for TAD boundary function.
- A model of temporal loop extrusion blocking by multiple CTCF sites explains strong TAD insulation.
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