Identify Critical Genes in Development with Consistent H3K4me2 Patterns across Multiple Tissues

Histone modification is an important epigenetic event which plays essential roles in cell differentiation and tissue development. Recent studies show that a unique dimethylation of lysine 4 residue on histone 3 (H3K4me2) distribution pattern around transcription starting sites (TSS) of genes marks tissue specific genes in human CD4 þ T cells and mouse nervous tissue cells. However, existence of this pattern has not been widely tested and its implication remains unclear. In this paper, we study the H3K4me2 distribution patterns across six different cell lines from five major tissue types (including muscular tissue, nervous tissue, non-blood connective tissue, blood, and epithelial tissue) as well as embryonic stem cells. We define a metric ‘tail length’ to quantitatively describe H3K4me2 distribution patterns around the TSS. While confirming the previous observations, we also identified a group of 217 genes with ubiquitous long-tail H3K4me2 patterns in all the tested tissues and the embryonic stem cells (ESC). Further analyses confirmed that these genes are critical for development, and highly interactive with other tissue specific genes as evinced by protein-protein interaction networks, suggesting their critical regulatory functions. Our results suggest that rich information on gene functions and epigenetic events can be revealed using pattern recognition methods.