Differential H3K4me3 Domains in Normal and Colorectal Cancer Cells Reveal Novel Epigenetic Targets

Histone H3 trimethylated at lysine 4 (H3K4me3) is an histone mark associated with transcriptionally active genes. H3K4me3 has two types of distribution: a sharp distribution of approximately 500 bp and a broad H3K4me3 domain that may extend 4 kb and longer through the gene body. Most transcribed genes have a narrow H3K4me3 configuration, whereas genes involved in cell identity and tumor suppression have a broad arrangement in normal cells. In cancer cells, genes that promote cancer possess a broad H3K4me3 domain. In this study, we performed H3K4me3 chromatin immunoprecipitation sequencing to determine the genes with narrow and broad H3K4me3 configurations in normal colon epithelial cells and three colon cancer cell lines. The analysis revealed that genes involved in cell adhesion and nervous system development had an H3K4me3 peak next to their transcription start site in normal cells but not in colon cancer cells. Genes coding for long non-coding RNA (lncRNA) were differentially marked with a broad H3K4me3 domain in normal colon versus colon cancer cells (FENDRR in normal colon; ELFN1-AS1 in colon cancer). Identifying the genes that are silenced or activated, particularly in colon cancer, provides a list of actionable targets for designing effective treatments for this prevalent human disease.