Study suggests some CpGs in the genome can be hemimethylated by design

March 9, 2018 by Bob Yirka, Medical Xpress report
Credit: CC0 Public Domain

A pair of researchers at Emory University has found that some CpGs in the genome can be hemimethylated by design, rather than by chance. In their paper published in the journal Science, Chenhuan Xu and Victor Corces describe their study of DNA methylation and the fate of hemimethylated DNA in daughter strands after replication. Jafar Sharif and Haruhiko Koseki with the Developmental Genetics Group, Center for Integrative Medical Sciences in Japan offer a Perspective piece on the work done by the team in the same journal issue.

DNA methylation (when methyl groups are added to the DNA molecule) is a modification that serves to regulate gene transcription, embryonic development, and cell differentiation in plants and animals. In animals, specifically mammals, methylation happens at the CpG dinucleotides symmetrically, which results in corresponding cytosine residue on the CpG components. But, as the researchers note, this process is halted during replication, a period during which a daughter strand that is unmethylated and a methylated parent strand work in conjunction to create a methylated CpG dyad. This is called hemimethylated DNA.

Prior research has shown that such hemimethylated DNA generally tends to fully methylate, or in some cases, to unmethylate by dilution. But approximately 10 percent of trophoblast or embryonic stems cells remain hemimethylated. Until now, it has been a mystery whether this occurs by simple chance or if there is some other process at work. In this new effort, the researchers discovered that at least some of these instances are due to design. Furthermore, they found that hemimethylated instances are inherited and happen over the course of several cell divisions.

To learn more about the process, the team mapped the DNA methylome that was targeted by three types of DNA methyltransferases, which showed some of the interactions that occur between DNMIs and daughter cytosines. They also showed inheritance of hemiCpGs at binding sites in pluripotent cells. More specifically, they found that during replication, at the fork, hemimethylated DNA is held by UHRF1, a reader protein, and thereafter, DMNT1 was recruited, which served to convert CpGs to symmetrical methylation. This resulted in reinstating the original methylation symmetrical pattern that existed prior to replication. They found also that DNMT1-bound emerging DNA fragments were overwhelmingly hemimethylated. They that it was elimination of the cause of hemimethylation factors that resulted in the frequency of , which, they claim, suggests that hemimethylation might actually serve as means for stabilizing chromatin interactions.

Explore further: DNA methylation in adulthood linked to season of birth

More information: Chenhuan Xu et al. Nascent DNA methylome mapping reveals inheritance of hemimethylation at CTCF/cohesin sites, Science (2018). DOI: 10.1126/science.aan5480

The faithful inheritance of the epigenome is critical for cells to maintain gene expression programs and cellular identity across cell divisions. We mapped strand-specific DNA methylation after replication forks and show maintenance of the vast majority of the DNA methylome within 20 minutes of replication and inheritance of some hemimethylated CpG dinucleotides (hemiCpGs). Mapping the nascent DNA methylome targeted by each of the three DNA methyltransferases (DNMTs) reveals interactions between DNMTs and substrate daughter cytosines en route to maintenance methylation or hemimethylation. Finally, we show the inheritance of hemiCpGs at short regions flanking CCCTC-binding factor (CTCF)/cohesin binding sites in pluripotent cells. Elimination of hemimethylation causes reduced frequency of chromatin interactions emanating from these sites, suggesting a role for hemimethylation as a stable epigenetic mark regulating CTCF-mediated chromatin interactions.

Related Stories

DNA methylation in adulthood linked to season of birth

March 16, 2016
(HealthDay)—DNA methylation in adulthood is associated with season of birth and may influence the effect of season of birth on allergy, according to a study published online March 12 in Allergy.

New methodology tracks changes in DNA methylation in real time at single-cell resolution

September 24, 2015
Whitehead Institute researchers have developed a methodology to monitor changes in DNA methylation over time in individual cells.

Recommended for you

Scientists identify genes that could inform novel therapies for EBV-related cancers

March 20, 2018
VCU Massey Cancer Center researchers have identified two genes that are responsible for governing the replication of the Epstein-Barr virus, an infection that drives the growth of several types of cancer. The discovery could ...

Scientists discover how gene mutation reduces the need for sleep

March 19, 2018
It's every over-achiever's dream: a gene mutation that allows them to function normally with just four to six hours of sleep a night instead of the normal eight.

New osteoarthritis genes discovered

March 19, 2018
In the largest study of its kind, nine novel genes for osteoarthritis have been discovered by scientists from the Wellcome Sanger Institute and their collaborators. Results of the study, published today (19 March) in Nature ...

At-home genetic testing leads to misinterpretations of results

March 19, 2018
Home genetic tests like AncestryDNA and 23andMe are more popular than ever, with sales topping $99 million in 2017. But a new study led by a Boston University School of Public Health researcher highlights the potential negative ...

New methods find undiagnosed genetic diseases in electronic health records

March 15, 2018
Patients diagnosed with heart failure, stroke, infertility and kidney failure could actually be suffering from rare and undiagnosed genetic diseases.

Hundreds of genes linked to intelligence in global study

March 14, 2018
More than 500 genes linked to intelligence have been identified in the largest study of its kind. Scientists compared variation in DNA in more than 240,000 people from around the world, to discover which genes are associated ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.