Journal
DEVELOPMENT
Volume 141, Issue 6, Pages 1313-U255Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.104646
Keywords
Epigenetics; DNA methylation; Imprinting
Categories
Funding
- Invest Northern Ireland [POC206]
- Medical Research Council [MR/J007773/1]
- MRC [MR/J007773/1] Funding Source: UKRI
- Medical Research Council [MR/J007773/1] Funding Source: researchfish
Ask authors/readers for more resources
A functional role for DNA methylation has been well-established at imprinted loci, which inherit methylation uniparentally, most commonly from the mother via the oocyte. Many CpG islands not associated with imprinting also inherit methylation from the oocyte, although the functional significance of this, and the common features of the genes affected, are unclear. We identify two major subclasses of genes associated with these gametic differentially methylated regions (gDMRs), namely those important for brain and for testis function. The gDMRs at these genes retain the methylation acquired in the oocyte through preimplantation development, but become fully methylated postimplantation by de novo methylation of the paternal allele. Each gene class displays unique features, with the gDMR located at the promoter of the testis genes but intragenically for the brain genes. Significantly, demethylation using knockout, knockdown or pharmacological approaches in mouse stem cells and fibroblasts resulted in transcriptional derepression of the testis genes, indicating that they may be affected by environmental exposures, in either mother or offspring, that cause demethylation. Features of the brain gene group suggest that they might represent a pool from which many imprinted genes have evolved. The locations of the gDMRs, as well as methylation levels and repression effects, were also conserved in human cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available