(Press-News.org) Researchers from the University of Cambridge and the Babraham Institute have found that a naturally occurring modified DNA base appears to be stably incorporated in the DNA of many mammalian tissues, possibly representing an expansion of the functional DNA alphabet.
The new study, published today (22 June) in the journal Nature Chemical Biology, has found that this rare 'extra' base, known as 5-formylcytosine (5fC) is stable in living mouse tissues. While its exact function is yet to be determined, 5fC's physical position in the genome makes it likely that it plays a key role in gene activity.
'This modification to DNA is found in very specific positions in the genome -- the places which regulate genes,' said the paper's lead author Dr. Martin Bachman, who conducted the research while at Cambridge's Department of Chemistry. 'In addition, it's been found in every tissue in the body -- albeit in very low levels.'
'If 5fC is present in the DNA of all tissues, it is probably there for a reason,' said Professor Shankar Balasubramanian of the Department of Chemistry and the Cancer Research UK Cambridge Institute, who led the research. 'It had been thought this modification was solely a short-lived intermediate, but the fact that we've demonstrated it can be stable in living tissue shows that it could regulate gene expression and potentially signal other events in cells.'
Since the structure of DNA was discovered more than 60 years ago, it's been known that there are four DNA bases: G, C, A and T (Guanine, Cytosine, Adenine and Thymine). The way these bases are ordered determines the makeup of the genome.
In addition to G, C, A and T, there are also small chemical modifications, or epigenetic marks, which affect how the DNA sequence is interpreted and control how certain genes are switched on or off. The study of these marks and how they affect gene activity is known as epigenetics.
5fC is one of these marks, and is formed when enzymes called TET enzymes add oxygen to methylated DNA -- a DNA molecule with smaller molecules of methyl attached to the cytosine base. First discovered in 2011, it had been thought that 5fC was a 'transitional' state of the cytosine base which was then being removed from DNA by dedicated repair enzymes. However, this new research has found that 5fC can actually be stable in living tissue, making it likely that it plays a key role in the genome.
Using high-resolution mass spectrometry, the researchers examined levels of 5fC in living adult and embryonic mouse tissues, as well as in mouse embryonic stem cells - the body's master cells which can become almost any cell type in the body.
They found that 5fC is present in all tissues, but is very rare, making it difficult to detect. Even in the brain, where it is most common, 5fC is only present at around 10 parts per million or less. In other tissues throughout the body, it is present at between one and five parts per million.
The researchers applied a method consisting of feeding cells and living mice with an amino acid called L-methionine, enriched for naturally occurring stable isotopes of carbon and hydrogen, and measuring the uptake of these isotopes to 5fC in DNA. The lack of uptake in the non-dividing adult brain tissue pointed to the fact that 5fC can be a stable modification: if it was a transient molecule, this uptake of isotopes would be high.
The researchers believe that 5fC might alter the way DNA is recognised by proteins. 'Unmodified DNA interacts with a specific set of proteins, and the presence of 5fC could change these interactions either directly or indirectly by changing the shape of the DNA duplex,' said Bachman. 'A different shape means that a DNA molecule could then attract different proteins and transcription factors, which could in turn change the way that genes are expressed.'
'This will alter the thinking of people in the study of development and the role that these modifications may play in the development of certain diseases,' said Balasubramanian. 'While work is continuing in determining the exact function of this 'extra' base, its position in the genome suggests that it has a key role in the regulation of gene expression.'
INFORMATION:
The research was supported by Cancer Research UK, the Wellcome Trust and the Biotechnology and Biological Sciences Research Council UK.
Researchers from the University of Cambridge, together with French collaborators based in Toulouse, have developed a new method to see inside battery-like devices known as supercapacitors at the atomic level. The new method could be used in order to optimise and improve the devices for real-world applications, including electric cars, where they can be used alongside batteries to enhance a vehicle's performance.
By using a combination of nuclear magnetic resonance (NMR) spectroscopy and tiny scales sensitive enough to detect changes in mass of a millionth of a gram, ...
More than half of long-term smokers and ex-smokers who are considered disease-free because they passed lung-function tests have respiratory-related impairments when more closely evaluated with lung imaging, walking and quality-of-life tests. Many of those people likely have the earliest stages of chronic obstructive pulmonary disease, an incurable progressive disease (COPD) that is the third leading cause of death in the United States.
"The impact of chronic smoking on the lungs and the individual is substantially underestimated when using lung-function tests alone," ...
A gene previously suspected of wielding the single greatest genetic influence on human obesity actually has nothing to do with body weight, according to a new study led by researchers at Harvard Medical School and Boston Children's Hospital.
The work not only overturns a major finding about the genetics of obesity but also provides the first effective ways to analyze "particularly ornery and confusing" parts of the genome, such as the locus of this gene, said the study's co-senior author, Steven McCarroll, assistant professor of genetics at HMS.
The techniques described ...
In 2002, archaeologists discovered the jawbone of a human who lived in Europe about 40,000 years ago. Geneticists have now analyzed ancient DNA from that jawbone and learned that it belonged to a modern human whose recent ancestors included Neanderthals.
Neanderthals lived in Europe until about 35,000 years ago, disappearing at the same time modern humans were spreading across the continent. The new study, co-led by Howard Hughes Medical Institute (HHMI) investigator David Reich at Harvard Medical School and Svante Pääbo at the Max Planck Institute in Germany, ...
The island Isla Santa María in the south of central Chile is the document of a complete seismic cycle.
Charles Darwin and his captain Robert Fitzroy witnessed the great earthquake of 1835 in south central Chile. The „Beagle"-Captain's precise measurements showed an uplift of the island Isla Santa María of 2 to 3 meters after the earthquake. What Darwin and Fitzroy couldn't know was the fact that 175 years later nearly at the same position such a strong earthquake would recur.
At the South American west coastline the Pacific Ocean floor moves under the ...
Originally it became famous as an anesthetic gas used by dentists. However, laughing gas, or chemically correct nitrous oxide, is also found in large quantities in nature and has serious effects on climate: In the lower atmosphere it is a strong greenhouse gas, and in higher layers of the atmosphere it contributes indirectly to the destruction of ozone. "A global assessment of marine nitrous oxide emissions is, however, difficult because we do not know exactly where and how much nitrous oxide is produced," says marine chemist Damian L. Arévalo-Martínez from GEOMAR ...
Despite the passage of Georgia's Smokefree Air Act in 2005, the number of restaurants and bars that allow smoking has doubled in recent years, according to researchers at Georgia State University's School of Public Health.
Researchers found a significant number of restaurant and bar owners have taken advantage of exemptions in the laws to create smoking zones.
"The increase in smoking-allowed establishments may be attributed to the increase in the percentage of establishments permitting smoking in designated dining areas and the large percentage of establishments that ...
Virginia Tech engineers have shed light on what happens to a nearby particle when bubbles burst.
Sunghwan Jung, an assistant professor of biomedical engineering and mechanics in the College of Engineering, has discovered new information about a phenomenon called cavitation, the process of bubble formation in a fluid like water.
These bubbles eventually collapse under the pressure of the surrounding fluid, sending out pressure waves that can affect anything nearby. For example, shrimp use cavitation bubbles to hunt because the waves can kill small fish.
Cavitation ...
A team of Massachusetts General Hospital (MGH) researchers has found a way to expand the use and precision of the powerful gene-editing tools called CRISPR-Cas9 RNA-guided nucleases. In their report receiving advance online release in Nature, the investigators describe evolved versions of the DNA-cutting Cas9 enzyme that are able to recognize a different range of nucleic acid sequences than is possible with the naturally occurring form of Cas9 that has been used to date.
"In our paper we show that sites in human and zebrafish genes that could not previously be modified ...
COLLEGE PARK, Md. - Doctors have many concerns about online crowdsourced ratings, which are intended to make patients better-informed consumers of health care, but this is a big one: They worry that complainers will be the most outspoken contributors to rating sites, skewing scores and resulting in a kind of heckler's veto.
A new study from the Robert H. Smith School of Business at the University of Maryland finds that that fear is unwarranted. Researchers compared the ratings of 1,425 doctors in three metropolitan areas -- Denver, Kansas City and Memphis -- on the popular ...
