Functional human genes typically exhibit epigenetic conservation

• Published in: PloS one Vol. 16; no. 9; p. e0253250
• Main Authors: Rud, Daniel, Marjoram, Paul, Siegmund, Kimberly, Shibata, Darryl
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.09.2021; Public Library of Science (PLoS)
• Subjects: Analysis; Biology and Life Sciences; Cell culture; Cell Culture Techniques - methods; Cell Line, Tumor; Cell lines; Colorectal cancer; Conservation; CRISPR; Crypts; Deoxyribonucleic acid; DNA; DNA Methylation; Epigenesis, Genetic; Epigenetic inheritance; Epigenetics; Gene expression; Gene Expression Regulation; Genes; Genes, Essential; Genetic Drift; Genomes; Human tissues; Humans; Medicine and Health Sciences; Methylation; Observations; Preventive medicine; Research and Analysis Methods; Tissue culture; United States; Los Angeles California; United States > US; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0253250

Recent DepMap CRISPR-Cas9 single gene disruptions have identified genes more essential to proliferation in tissue culture. It would be valuable to translate these finding with measurements more practical for human tissues. Here we show that DepMap essential genes and other literature curated functional genes exhibit cell-specific preferential epigenetic conservation when DNA methylation measurements are compared between replicate cell lines and between intestinal crypts from the same individual. Culture experiments indicate that epigenetic drift accumulates through time with smaller differences in more functional genes. In NCI-60 cell lines, greater targeted gene conservation correlated with greater drug sensitivity. These studies indicate that two measurements separated in time allow normal or neoplastic cells to signal through conservation which human genes are more essential to their survival in vitro or in vivo.