Researchers extend human epigenomic map

August 8, 2013

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 sapien 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., , , , etc.) can have an identical compliment 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 (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."

Explore further: Scientists complete first mapping of molecule found in human embryonic stem cells

Related Stories

Scientists complete first mapping of molecule found in human embryonic stem cells

July 21, 2011
Stem cell researchers at UCLA have generated the first genome-wide mapping of a DNA modification called 5-hydroxymethylcytosine (5hmC) in embryonic stem cells, and discovered that it is predominantly found in genes that are ...

Research uncovers dynamic changes in the epigenome that occur during brain circuitry formation

July 4, 2013
Changes in the epigenome, including chemical modifications of DNA, can act as an extra layer of information in the genome, and are thought to play a role in learning and memory, as well as in age-related cognitive decline. ...

Ills of aging blood: Short-circuited stem cell programming linked to failing blood development

February 15, 2013
As blood stem cells age, changes in the epigenome—the system that regulates which genes are switched on and which are switched off throughout the body—alter these cells in ways that lead to reduced immune response, increased ...

Search for epigenetic decoder leads scientists to Rett Syndrome

December 21, 2012
(Medical Xpress)—A few years ago, scientists discovered an unexpected layer of information woven into the genetic code – a nucleotide called 5-hydroxymethylcytosine, or 5hmC. Its meaning was unknown at the time, but a ...

Recommended for you

Genome analysis with near-complete privacy possible, say researchers

August 17, 2017
It is now possible to scour complete human genomes for the presence of disease-associated genes without revealing any genetic information not directly associated with the inquiry, say Stanford University researchers.

Science Says: DNA test results may not change health habits

August 17, 2017
If you learned your DNA made you more susceptible to getting a disease, wouldn't you work to stay healthy?

Genetic variants found to play key role in human immune system

August 16, 2017
It is widely recognized that people respond differently to infections. This can partially be explained by genetics, shows a new study published today in Nature Communications by an international collaboration of researchers ...

Phenotype varies for presumed pathogenic variants in KCNB1

August 16, 2017
(HealthDay)—De novo KCNB1 missense and loss-of-function variants are associated with neurodevelopmental disorders, with or without seizures, according to a study published online Aug. 14 in JAMA Neurology.

Active non-coding DNA might help pinpoint genetic risk for psychiatric disorders

August 16, 2017
Northwestern Medicine scientists have demonstrated a new method of analyzing non-coding regions of DNA in neurons, which may help to pinpoint which genetic variants are most important to the development of schizophrenia and ...

Evolved masculine and feminine behaviors can be inherited from social environment

August 15, 2017
The different ways men and women behave, passed down from generation to generation, can be inherited from our social environment - not just from genes, experts have suggested.

0 comments

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.