Cell type- and transcription-independent spatial proximity between enhancers and promoters

Author:

Mian Yasmine1,Wang Li1,Keikhosravi Adib1,Guo Konnie1,Misteli Tom1,Arda H. Efsun1,Finn Elizabeth H.12ORCID

Affiliation:

1. National Cancer Institute, National Institutes of Health, Bethesda, MD 20892

2. Cell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104

Abstract

Cell type–specific enhancers are critically important for lineage specification. The mechanisms that determine cell-type specificity of enhancer activity, however, are not fully understood. Most current models for how enhancers function invoke physical proximity between enhancer elements and their target genes. Here, we use an imaging-based approach to examine the spatial relationship of cell type–specific enhancers and their target genes with single-cell resolution. Using high-throughput microscopy, we measure the spatial distance from target promoters to their cell type–specific active and inactive enhancers in individual pancreatic cells derived from distinct lineages. We find increased proximity of all promoter-enhancer pairs relative to non-enhancer pairs separated by similar genomic distances. Strikingly, spatial proximity between enhancers and target genes was unrelated to tissue-specific enhancer activity. Furthermore, promoter-enhancer proximity did not correlate with the expression status of target genes. Our results suggest that promoter-enhancer pairs exist in a distinctive chromatin environment but that genome folding is not a universal driver of cell-type specificity in enhancer function.

Publisher

American Society for Cell Biology (ASCB)

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