DNA methylation in blood-Potential to provide new insights into cell biology

PLoS One. 2020 Nov 4;15(11):e0241367. doi: 10.1371/journal.pone.0241367. eCollection 2020.

Abstract

Epigenetics plays a fundamental role in cellular development and differentiation; epigenetic mechanisms, such as DNA methylation, are involved in gene regulation and the exquisite nuance of expression changes seen in the journey from pluripotency to final differentiation. Thus, DNA methylation as a marker of cell identify has the potential to reveal new insights into cell biology. We mined publicly available DNA methylation data with a machine-learning approach to identify differentially methylated loci between different white blood cell types. We then interrogated the DNA methylation and mRNA expression of candidate loci in CD4+, CD8+, CD14+, CD19+ and CD56+ fractions from 12 additional, independent healthy individuals (6 male, 6 female). 'Classic' immune cell markers such as CD8 and CD19 showed expected methylation/expression associations fitting with established dogma that hypermethylation is associated with the repression of gene expression. We also observed large differential methylation at loci which are not established immune cell markers; some of these loci showed inverse correlations between methylation and mRNA expression (such as PARK2, DCP2). Furthermore, we validated these observations further in publicly available DNA methylation and RNA sequencing datasets. Our results highlight the value of mining publicly available data, the utility of DNA methylation as a discriminatory marker and the potential value of DNA methylation to provide additional insights into cell biology and developmental processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / metabolism
  • CpG Islands / genetics
  • DNA Methylation / genetics*
  • Epigenesis, Genetic
  • Female
  • Humans
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Molecular Sequence Annotation
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reproducibility of Results

Substances

  • Biomarkers
  • RNA, Messenger

Grants and funding

The study was supported in part by funding provided by the Wellington Medical Research Foundation (https://researchforlife.org.nz/) grant number 2015/255 awarded to MB. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. There was no additional external funding received for this study.