High-resolution dissection of human cell type-specific enhancers in cis and trans activities

The spatiotemporal-specific gene expression is regulated by cell type-specific regulatory elements. Here we selected the H3K4me1-associated DNA sequences as candidate enhancers in two different human cell lines and performed ChIP-STARR-seq to quantify the cell-type-specific enhancer activities with high-resolution. We investigated how the activity landscape of enhancers would change when transferred from native cells (cis activity) to another cell lines (trans activity). We obtained enhancers cis activity maps and trans activity maps in two different cell lines. The cis and trans activity maps enabled us to identify cell type-specific active enhancers, with enrichment of motifs of differentially expressed TFs. Comparisons between the cis and trans activity maps revealed general consistent regulatory property with different levels of activity in two cell lines, suggesting sequence intrinsic regulatory properties remain similar in different types of cells. This study provides a new perspective on sequence intrinsic enhancer activities in different types of cells.