Dynamic CTCF binding directly mediates interactions among cis-regulatory elements essential for hematopoiesis

Area of Science:

• Genomics
• Epigenetics
• Molecular Biology

Background:

• Constitutive CCCTC-binding factor (CTCF) sites maintain chromatin structures.
• The role of CTCF in cell-type-specific transcription is not well understood.

Purpose of the Study:

• To investigate the function of CTCF in gene regulation during blood cell development.
• To identify dynamic, cell-type-specific CTCF binding sites.

Main Methods:

• Examined CTCF occupancy in primary blood cells.
• Utilized CRISPR-Cas9 for perturbation experiments.
• Analyzed CTCF-binding motifs and enhancer-promoter interactions.

Main Results:

• Identified dynamic, cell-type-specific CTCF binding sites colocalizing with lineage-specific transcription factors.
• Found these sites enriched for SNPs associated with blood cell traits.
• Demonstrated CTCF's critical role in red blood cell development and erythropoiesis via perturbation experiments.
• Showed deletion of CTCF motifs abolished enhancer-promoter interactions for erythroid genes like RBM38, causing abnormal erythropoiesis.

Conclusions:

• CTCF has a novel, cell-type-specific function in facilitating interactions between distal regulatory elements and target promoters.
• Dynamic CTCF binding is crucial for transcriptional regulation during hematopoiesis.