Lifestyle Influences Metabolism Via DNA Methylation

An unhealthy lifestyle leaves traces in the DNA. These may have specific effects on metabolism, causing organ damage or disease. Scientists of Helmholtz Zentrum München have now identified 28 DNA alterations associated with metabolic traits. This world-first epigenome-wide association study (EWAS) of modified genes and metabolites has been now published in the journal Human Molecular Genetics.

In the course of life, aging processes, environmental influences and lifestyle factors such as smoking or diet induce biochemical alterations to the DNA. Frequently, these lead to DNA methylation, a process in which methyl groups are added to particular DNA segments, without changing the DNA sequence. Such processes can influence gene function and are known as epigenetics. Scientists of the Institute of Genetic Epidemiology (IGE) and the Research Unit Molecular Epidemiology (AME) at Helmholtz Zentrum München are seeking to determine what association exists between these epigenetic processes and the health consequences, in particular for the metabolism.

To this end, the team led by Christian Gieger (IGE) and Melanie Waldenberger (AME), in in collaboration with Karsten Suhre of Weill Cornell Medical College in Qatar analyzed blood samples from more than 1800 participants of the KORA study *. In doing so, they analyzed more than 457,000 loci in the DNA as to biochemical alterations and compared them with the concentrations of 649 different metabolites. The analysis showed that the methylation of 28 DNA segments changed a number of important metabolic processes.

In the relevant DNA regions there were also already known disease-related genes: for example, the TXNIP gene that regulates glucose metabolism and is associated with the development of diabetes mellitus. Appropriately, with the methylated TXNIP there were altered concentrations of metabolites from the lipid and glucose metabolism. Also genes that are known to be biochemically altered due to smoking affect different metabolic activities, and specifically those with corresponding biological functions.

"This study gives us new insights into how lifestyle factors can influence metabolism via the resulting alterations in the DNA," said Gieger, research group leader at the IGE. "We can now use these results to develop new diagnostic and therapeutic approaches for lifestyle-related diseases such as diabetes."

Tomado de: Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health. "Lifestyle Influences Metabolism via DNA Methylation." ScienceDaily, 20 Sep. 2013. Web. 23 Sep. 2013.

Researchers Extend Human Epigenomic Map

Ten years ago, scientists announced the end of the Human Genome Project, the international attempt to learn which combination of four nucleotides -- adenine, thymine, cytosine, and guanine -- is unique to Homo sapiens DNA. This biological alphabet helped researchers identify the approximately 25,000 genes coded in the human genome, but as time went on, questions arose about how all of these genes are controlled.

Now, Harvard Stem Cell Institute Principal Faculty member Alexander Meissner, PhD, reports another milestone, this time contributing to the multilayered NIH-funded human Roadmap Epigenomics Project. Epigenetics is the study of how the over 200 human cell types (e.g., muscle cells, nerve cells, liver cells, etc.) can have an identical complement of genes but express them differently. Part of the answer lies in the way that DNA is packaged, with tight areas silencing genes and open areas allowing for genes to be translated into proteins. Stem cells differentiate into various cell types by marking specific genes that will be open and closed after division.

New research by Meissner, published online as a letter in the journal Nature, describes the dynamics of DNA methylation across a wide range of human cell types. Chemically, these marks are the addition of a methyl group -- one carbon atom surrounded by three hydrogen atoms (CH3) -- anywhere a cytosine nucleotide sits next to a guanine nucleotide in the DNA sequence.

Meissner's team, led by graduate student Michael Ziller, at Harvard's Department of Stem Cell and Regenerative Biology mapped nearly all of the 28-million cytosine-guanine pairings among the 3-billion nucleotides that make up human DNA, and then wanted to know which of these 28 million are dynamic or static across all the cell types.

"When we asked, how many of them are changing, the answer was a very small fraction," said Meissner. The researchers found that eighty percent of the 28-million cytosine-guanine pairs are largely unchanged and might not participate in the regulation of the cell types, while the dynamic ones sit at sites that are relevant for gene expression -- in particular distal regulatory sites such as enhancers. "Importantly this allows us to improve our current approaches of mapping this important mark through more targeted strategies that still capture most of the dynamics," Meissner said.

The methylation map generated by the Meissner lab is part of a larger National Institutes of Health (NIH) consortium to look at all of the different epigenetic modification that are found across a large number of human cell and tissue types. Earlier this year, the Meissner's lab recorded all of the gene expression and multi-layered epigenetic dynamics that take place in early stem cell differentiation when they prepare to divide into their next fated cell type.

In addition to his roles at Harvard, Meissner is affiliated with the Broad Institute and the New York Stem Cell Foundation. Only a graduate student in 2007, he has quickly established himself as a leader in the epigenetics field. "It just happens to be that we're at the right time and at the right place, both physically and sort of in time, " he said. "Just five years ago, we would have had the same question, but we wouldn't have had the same tools to answer the question."

Harvard University. "Researchers extend human epigenomic map." ScienceDaily, 8 Aug. 2013. Web. 14 Sep. 2013.