RT Journal Article
SR Electronic
T1 CpG traffic lights are markers of regulatory regions in humans
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 095968
DO 10.1101/095968
A1 Abdullah M. Khamis
A1 Anna V. Lioznova
A1 Artem V. Artemov
A1 Vasily Ramensky
A1 Vladimir B. Bajic
A1 Yulia A Medvedeva
YR 2016
UL http://biorxiv.org/content/early/2016/12/28/095968.abstract
AB DNA methylation is involved in regulation of gene expression. Although modern methods profile DNA methylation at single CpG sites, methylation levels are usually averaged over genomic regions in the downstream analyses. In this study we demonstrate that single CpG methylation can serve as a more accurate predictor of gene expression compared to average promoter / gene body methylation. CpG positions with significant correlation between methylation and expression of a gene nearby (called CpG traffic lights) are evolutionary conserved and enriched for exact TSS positions and active enhancers. Among all promoter types, CpG traffic lights are especially enriched in poised promoters. Genes that harbor CpG traffic lights are associated with development and signal transduction. Methylation levels of individual CpG traffic lights vary between cell types dramatically with the increased frequency of intermediate methylation levels, indicating cell population heterogeneity in CpG methylation levels Being in line with the concept of the inherited stochastic epigenetic variation, methylation of such CpG positions might contribute to transcriptional regulation. Alternatively, one can hypothesize that traffic lights are markers of absent gene expression resulting from inactivation of their regulatory elements. In any case, CpG traffic light mechanism provide a promising insight into enhancer activity and gene expression, important from both fundamental and practical points of view.