Cell Type-Specific Chromatin Signatures Underline Regulatory DNA Elements in Human Induced Pluripotent Stem Cells and Somatic Cells

Regulatory DNA elements in the human genome play important roles in determining the transcriptional abundance and spatiotemporal gene expression. It is a mystery how chromatin marks in regulatory elements are modulated to establish cell type-specific gene expression. Here we profiled a variety of epigenetic marks in the regulatory elements using massive ChIP-seq (n=84). We uncovered two classes of regulatory elements: Class I was identified with ubiquitous enhancer (H3K4me1) and promoter (H3K4me3) marks in all cell types, whereas Class II was enriched with H3K4me1 and H3K4me3 in a cell type-specific manner. For common genes regulated by both promoters and enhancers, Class I promoters displayed dominant regulatory effects on transcriptional abundance. Moreover, human iPSCs and somatic cells selected their preferential regulatory elements to maintain cell type-specific gene expression. Our study provides valuable resources for deciphering the epigenetic modulation of regulatory elements that fine-tune spatiotemporal gene expression in human development and diseases. Overall design: Large scale RNA-seq (n=6) and ChIP-seq (n=84) of 12 human cell lines, including fibroblast cells (FBs), endothelial cells (ECs), cardiac progenitor cells (CPCs), and induced pluripotent stem cells (iPSCs).