Posts Tagged ‘methylation’

A new Northwestern University study challenges prevailing understandings of genes as immutable features of biology that are fixed at conception.

Previous research has shown that socioeconomic status (SES) is a powerful determinant of human health and disease, and social inequality is a ubiquitous stressor for human populations globally. Lower educational attainment and/or income predict increased risk for heart disease, diabetes, many cancers and infectious diseases, for example. Furthermore, lower SES is associated with physiological processes that contribute to the development of disease, including chronic inflammation, insulin resistance and cortisol dysregulation.

In this study, researchers found evidence that poverty can become embedded across wide swaths of the genome. They discovered that lower socioeconomic status is associated with levels of DNA methylation (DNAm) — a key epigenetic mark that has the potential to shape gene expression — at more than 2,500 sites, across more than 1,500 genes.

In other words, poverty leaves a mark on nearly 10 percent of the genes in the genome.

Lead author Thomas McDade said this is significant for two reasons.

“First, we have known for a long time that SES is a powerful determinant of health, but the underlying mechanisms through which our bodies ‘remember’ the experiences of poverty are not known,” said McDade, professor of anthropology in the Weinberg College of Arts and Sciences at Northwestern and director of the Laboratory for Human Biology Research.

“Our findings suggest that DNA methylation may play an important role, and the wide scope of the associations between SES and DNAm is consistent with the wide range of biological systems and health outcomes we know to be shaped by SES.”

Secondly, said McDade, also a faculty fellow at Northwestern’s Institute for Policy Research, experiences over the course of development become embodied in the genome, to literally shape its structure and function.

“There is no nature vs. nurture,” he adds.

McDade said he was surprised to find so many associations between socioeconomic status and DNA methylation, across such a large number of genes.

“This pattern highlights a potential mechanism through which poverty can have a lasting impact on a wide range of physiological systems and processes,” he said.

Follow-up studies will be needed to determine the health consequences of differential methylation at the sites the researchers identified, but many of the genes are associated with processes related to immune responses to infection, skeletal development and development of the nervous system.

“These are the areas we’ll be focusing on to determine if DNA methylation is indeed an important mechanism through which socioeconomic status can leave a lasting molecular imprint on the body, with implications for health later in life,” McDade said.

###

“Genome-wide analysis of DNA methylation in relation to socioeconomic status during development and early adulthood” published recently in the American Journal of Physical Anthropology.

In addition to McDade, co-authors include Calen P. Ryan, Northwestern; Meaghan J. Jones, University of British Columbia; Morgan K. Hoke, University of Pennsylvania; Judith Borja, University of San Carlos; Gregory E. Miller and Christopher W. Kuzawa of Northwestern; and Michael S. Kobor, University of British Columbia.

https://www.eurekalert.org/pub_releases/2019-04/nu-pla040419.php

Thanks to Kebmodee for bringing this to the It’s Interesting community.

Advertisements

Methyl chemical groups dot lengths of DNA, helping to control when certain genes are accessible by a cell. In new research, UCLA scientists have shown that at the connections between brain cells—which often are located far from the central control centers of the cells—methyl groups also dot chains of RNA. This methyl markup of RNA molecules is likely key to brain cells’ ability to quickly send signals to other cells and react to changing stimuli in a fraction of a second.

To dictate the biology of any cell, DNA in the cell’s nucleus must be translated into corresponding strands of RNA. Next, the messenger RNA, or mRNA—an intermediate genetic molecule between DNA and proteins—is transcribed into proteins. If a cell suddenly needs more of a protein—to adapt to an incoming signal, for instance—it must translate more DNA into mRNA. Then it must make more proteins and shuttle them through the cell to where they are needed. This process means that getting new proteins to a distant part of a cell, like the synapses of neurons where signals are passed, can take time.

Research has recently suggested that methyl chemical groups, which can control when DNA is transcribed into mRNA, are also found on strands of mRNA. The methylation of mRNA, researchers hypothesize, adds a level of control to when the mRNA can be translated into proteins, and their occurrence has been documented in a handful of organs throughout the bodies of mammals. The pattern of methyls on mRNA in any given cell is dubbed the “epitranscriptome.”

UCLA and Kyoto University researchers mapped out the location of methyls on mRNA found at the synapses, or junctions, of mouse brain cells. They isolated brain cells from adult mice and compared the epitranscriptome found at the synapses to the epitranscriptomes of mRNA elsewhere in the cells. At more than 4,000 spots on the genome, the mRNA at the synapse was methylated more often. More than half of these spots, the researchers went on to show, are in genes that encode proteins found mostly at the synapse. The researchers found that when they disrupted the methylation of mRNA at the synapse, the brain cells didn’t function normally.

The methylation of mRNA at the synapse is likely one of many ways that neurons speed up their ability to send messages, by allowing the mRNA to be poised and ready to translate into proteins when needed.

The levels of key proteins at synapses have been linked to a number of psychiatric disorders, including autism. Understanding how the epitranscriptome is regulated, and what role it plays in brain biology, may eventually provide researchers with a new way to control the proteins found at synapses and, in turn, treat disorders characterized by synaptic dysfunction.

More information: Daria Merkurjev et al. Synaptic N6-methyladenosine (m6A) epitranscriptome reveals functional partitioning of localized transcripts, Nature Neuroscience (2018). DOI: 10.1038/s41593-018-0173-6

Read more at: https://phys.org/news/2018-08-methyl-rna-key-brain-cell.html#jCp