DNA Methylation Involved in Gene Regulation in Human Cells Can also Be Digitized and Randomized

Every cell in our body shares the same genome and has the potential to become any type of cell. During development, the epigenome mediates the process by which cells become skin cells or neurons. If the genome is computer hardware, then the epigenome is the software that turns some genes on and makes other genes turn off to make cells become skin cells, or turn other genes on or off to make cells a neuron.

To a large extent, the epigenome is encoded as a set of cell type-specific DNA chemical modifications named  DNA methylation . In a new study, researchers from the National Institutes of Health Roadmap Epigenomics Project found that DNA methylation involved in gene regulation is largely digital and random, and the copies of the maternal and paternal genes in each cell are turned on or off for a certain period of time. Related research result is published in the Journal of Science.

Dr. Aleksandar Milosavljevic, co-director of the paper and co-director of the Center for Computational and Integrated Biomedical Research at Baylor College of Medicine, said that, ‘we want to better understand a cellular gene regulation mechanism called sequence-dependent, allele-specific methylation (SD-ASM), so we applied a method named whole-genome bisulfite sequencing (WGBS) which allows us to observe gene regulation at a single molecular resolution in a variety of human cell types so that we were able to determine  epigenetic differences in the same gene for parental and maternal chromosomes in a single cell.’

With this high-resolution approach, Milosavljevic and other researchers found that SD-ASM-mediated gene regulation works in a manner that is similar to a home thermostat but also has unique features. The thermostat has a pre-set temperature value at which the air conditioner will turn on, while the temperature is lower than this preset value, the air conditioner will be turned off. This process is digital, which means that the air conditioner is turned on or off and there is no intermediate activity. Also, the researchers found that this gene regulation mechanism is digital similar as the home thermostats, it will turn genes on or off for a fraction of the time, and there is no intermediate activity.

In terms of gene regulation mechanisms, specific genetic variants that control the paternal and maternal genes may represent different "preset temperature values" in the thermostat used for comparison, which results in differences in the extent of expression between the maternal and paternal gene copies in each human cell.