Fig. 4.

Male–female differences in DNA methylation and gene expression in X-linked genes. Scatter plot of DNA methylation values (β) on the y axis and genomic distances to the most proximal transcription start site are on the x axis. The lines indicate the average DNA methylation values (β) in males and on the female inactive X across the infection relevant tissues. A NKRF, an example of a gene subjected to X chromosome inactivation showed significantly higher DNA methylation levels in females compared to males. B DDX3X, an example of a gene with a high-density CpG island promoter was predicted to escape X chromosome inactivation and thus, the inactive X promoter DNA methylation levels in females were as low as male X promoter DNA methylation levels. C CA5B, an example of a gene that did not possess a high-density or an intermediate-density CpG island promoter and hence, the X chromosome inactivation status could not be reliably estimated. However, linear modeling between the male X and female inactive X showed that the female inactive X was more methylated across the 5’ untranslated region and along the gene body. D Correspondingly, CA5B gene demonstrated significantly higher expression in females relative to males.