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Analysis of chromatin accessbility in erythroid cells following CRISPR editing or ASO perturbation of BCL11A enhancer

ABSTRACT: CRISPR editing of an intronic enhancer within the BCL11A gene reactivates fetal hemoglobin (HbF) in adult erythroid cells, serving as a gene-based therapy for hemoglobinopathies. However, the mechanisms underlying the remarkable efficacy of CRISPR-mediated enhancer ablation remain poorly understood. We describe an evolutionarily conserved, enhancer-dependent chromatin architecture, the enhancer-CTCF rosette, essential for chromatin insulation and the developmental expression of BCL11A in hematopoiesis. CRISPR-mediated disruption of lineage-specific BCL11A enhancers impairs enhancer RNA transcription and NIPBL-cohesin loading, leading to destabilized chromatin configuration, impaired chromatin insulation, and epigenetic silencing of BCL11A. Antisense oligonucleotide-mediated depletion of enhancer RNA silences BCL11A by disrupting chromatin insulation in adult erythroid cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE292669 | GEO | 2025/11/13

REPOSITORIES: GEO

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