BioProject

DNA methylation has an impact on regulation of gene expression, however the relation between the two is complex. More...

DNA methylation has an impact on regulation of gene expression, however the relation between the two is complex. By performing an integrative analysis of the methylome and transcriptome of the four main circulating immune cell-subsets from healthy females, namely B cells, monocytes, CD4 and CD8 T cells, the relation between the two was characterized. In addition, in light of the known sex bias in the prevalence of several immune-mediated diseases, the female datasets were compared with similar public available male datasets. Immune subset-specific differentially methylated regions (DMRs) were found to be highly similar between males and females; however numerous sex-specific DMRs shared by the four leukocytes subsets were identified, most located on autosomal chromosomes. This provides a list of highly interesting candidate genes to be studied in diseases with sexual dimorphism like autoimmunity. Immune cell-specific DMRs were mainly located in the gene body and intergenic region, distant from CpG islands but overlapping with enhancer elements, thus indicating the importance of distal regulatory elements in leukocyte subsets. In contrast; sex-specific DMRs were over-represented in CpG islands, suggesting some difference in regulation between sex and immune-cell specificity. Both positive and negative correlations between cell-specific expression and methylation were observed, with negative correlation being more frequent. Our acquired immune cell- and sex- specific methylome and transcriptome profiles provide novel insight on their complex regulatory interactions, and may particularly contribute to research of immune-mediated diseases. Overall design: RNA purified from isolated 5 cell subsets (monocyte, B cells, CD4 T cells, CD8 T cells and PBMCs) obtained from 6 healthy female donors Less...