Landscape of Cohesin-Mediated Chromatin Loops in the Human Genome (ATAC-seq)

ABSTRACT: Physical interactions between distal regulatory elements in the genome play a key role in regulating gene expression, yet the extent to which these interactions vary between cell types and contribute to cell type-specific gene expression patterns remains unclear. To address this question we have mapped cohesin-bound chromatin loops in 24 diverse human cell types at high resolution using the chromatin interaction analysis by paired-end tag (ChIA-PET) sequencing approach. We combined a total of ~9.6 billion reads across all samples to generate a compendium of 124,830 loops, the most extensive resource currently available. We find that 39% of all chromatin loops vary across cell types, and such changes are effective at grouping cell types based on their tissue of origin, indicating commonalities in three-dimensional (3D) genome architecture amongst related cell types. In contrast, different cell types derived from the same individual show markedly different patterns of interactions indicating that the observed differences are mainly caused by epigenetic changes. Variation in chromatin loops correlates with changes in gene expression, especially for long-range contacts linking cell type-specific enhancers to promoters; moreover, genes contained within the same loop show coordinated co-expression changes in expression across cell types. We further find that loops specific to either blood or embryonic cell lines harbor distinct sets of genes relevant to cell type-specific function, and are enriched for lineage determining transcription factors, indicating a possible mechanism for the assembly of variable loops. Finally, we demonstrate that genetic variants identified in GWAS are enriched in variable loops in disease relevant cell types. Our results provide important insights in how changes in 3D chromatin organization potentially regulate cell type-specific functions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE139099 | GEO | 2020/07/23

REPOSITORIES: GEO