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HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries
Published on: March 31, 2019
CTCF binding site classes exhibit distinct evolutionary, genomic, epigenomic and transcriptomic features.
Kobby Essien1, Sebastien Vigneau, Sofia Apreleva
1Penn Center for Bioinformatics, Department of Genetics, 415 Curie Boulevard, University of Pennsylvania, Philadelphia, PA 19104, USA. kobby@pcbi.upenn.edu
Genome Biology
|November 20, 2009
Summary
CCCTC-binding factor (CTCF) sites in T cells fall into distinct classes. Low-occupancy CTCF sites show unique characteristics, including active histone marks and conserved flanking regions, suggesting specific functional roles.
Area of Science:
- Genomics
- Epigenetics
- Molecular Biology
Background:
- CCCTC-binding factor (CTCF) is an evolutionarily conserved protein regulating gene expression and chromatin structure.
- CTCF's diverse functions may stem from variations in its DNA-binding interactions.
- Understanding CTCF binding site classes is crucial for deciphering its functional diversity.
Purpose of the Study:
- Classify CTCF binding sites based on DNA-binding motif similarity.
- Characterize these classes using genomic, epigenomic, transcriptomic, and functional data.
- Investigate evolutionary conservation patterns across CTCF site classes.
Main Methods:
- Classification of ~26,000 CTCF binding sites in CD4+ T cells.
- Analysis of evolutionary, genomic, epigenomic, and transcriptomic features.
- Assessment of gene co-expression and histone modifications.
- Development of a novel class-conservation metric.
Main Results:
- Three distinct classes of CTCF sites were identified.
- Low-occupancy sites are cell-type specific, associated with active histone marks and higher gene expression.
- High-occupancy sites correlate with repressive marks and gene co-expression.
- Low-occupancy sites exhibit greater flanking region conservation and conserved occupancy across species.
Conclusions:
- CTCF occupancy defines distinct classes with differing functional roles.
- Low-occupancy CTCF sites play a critical and unique role in gene regulation.
- Conservation patterns suggest functional importance of specific CTCF site classes.
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