In 2009, the DNA alphabet expanded. Scientists discovered that an extra letter or "sixth nucleotide" was surprisingly abundant in DNA from stem cells and brain cells.
Now, researchers at Emory University School of Medicine have mapped the patterns formed by that letter in the brains of mice, observing how its pattern of distribution in the genome changes during development and aging.
Those patterns, stable or dynamic depending on the gene, suggest that 5-hydroxymethylcytosine (5-hmC) has its own distinct functions, which still need to be fully brought to light.
"Our data tells us that 5-hmC is not just an intermediate state," says senior author Peng Jin, PhD, associate professor of human genetics at Emory University School of Medicine. "It looks like it has specific functions in stem cells and brain. 5-hmC may poise a gene to be turned on after being repressed."
The results were published online Sunday by the journal Nature Neuroscience. The paper is the first report on how the patterns of 5-hmC's distribution change in mouse brain during development, and also contains data on 5-hmC in DNA samples from human brain.
Postdoctoral fellow Keith Szulwach and instructor Xuekun Li are co-first authors, and collaborators from the University of Chicago and the University of Wisconsin-Madison contributed to the paper.
5-hydroxymethylcytosine (5-hmC) is an epigenetic modification of cytosine, one of the four bases or "letters" making up DNA. Epigenetic modifications are changes in the way genes are turned on or off, but are not part of the underlying DNA sequence. 5-hmC resembles 5-methylcytosine (5-mC), another modified DNA base that scientists have been studying for decades. Until recently, chemical techniques did not allow scientists to tell the difference between them.
In contrast to 5-mC, 5-hmC appears to be enriched on active genes, especially in brain cells. 5-mC is generally found on genes that are turned off or on repetitive "junk" regions of the genome. When stem cells change into the cells that make up blood, muscle or brain, 5-mC helps shut off genes that aren't supposed to be turned on. Changes in 5-mC's distribution also underpin a healthy cell's transformation into a cancer cell.
It looks like 5-hmC can only appear on DNA where 5-mC already was present. This could be a clue that 5-hmC could be a transitory sign that the cell is going to remove a 5-mC mark. Jin says the patterns his team sees tell a different story, at least for some genes. On those genes, the level of 5-hmC is stably maintained and increases with age.
The Emory team used a method for chemically labeling 5-hmC they developed in cooperation with scientists at the University of Chicago. They find that 5-hmC is ten times more abundant in brain than in stem cells, and it is found more in the body of some genes, compared to stem cells.
In addition, the researchers found a relative lack of 5-hmC on X chromosomes in both males and females. That result is a surprise, Jin says, because it was already known that the X chromosome is subject to a special form of regulation in females only. Males have one X chromosome and females have two, and in female cells one of the X chromosomes is inactivated.
Jin's team is beginning to map how 5-hmC changes in neurological disorders, including Rett syndrome and autism, and refining techniques for detecting 5-hmC in DNA at high resolution.
The research was supported by the National Institutes of Health, the Simons Foundation and the Emory Genetics Discovery Initiative.
Reference: K.E. Szulwach et al 5-hydroxymethylcytosine–mediated epigenetic dynamics during postnatal neurodevelopment and aging. Nature Neuro. (2011).
Writer: Quinn Eastman
The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service.Learn more about Emory's health sciences:
Holly Korschun | EurekAlert!
Gene therapy shows promise for treating Niemann-Pick disease type C1
27.10.2016 | NIH/National Human Genome Research Institute
'Neighbor maps' reveal the genome's 3-D shape
27.10.2016 | International School of Advanced Studies (SISSA)
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
27.10.2016 | Materials Sciences
27.10.2016 | Physics and Astronomy
27.10.2016 | Life Sciences