Epigenetic discovery suggests DNA modifications more diverse than previously thought

cjb250 — Mon, 21 Dec 2015 15:54:31 +0000

Published today in the journal Nature Structural and Molecular Biology, the discovery suggests that many more DNA modifications than previously thought may exist in human, mouse and other vertebrates.

DNA is made up of four ‘bases’: molecules known as adenine, cytosine, guanine and thymine – the A, C, G and T letters. Strings of these letters form genes, which provide the code for essential proteins, and other regions of DNA, some of which can regulate these genes.

Epigenetics (epi - the Greek prefix meaning ‘on top of’) is the study of how genes are switched on or off. It is thought to be one explanation for how our environment and behaviour, such as our diet or smoking habit, can affect our DNA and how these changes may even be passed down to our children and grandchildren.

Epigenetics has so far focused mainly on studying proteins called histones that bind to DNA. Such histones can be modified, which can result in genes being switched on or of. In addition to histone modifications, genes are also known to be regulated by a form of epigenetic modification that directly affects one base of the DNA, namely the base C. More than 60 years ago, scientists discovered that C can be modified directly through a process known as methylation, whereby small molecules of carbon and hydrogen attach to this base and act like switches to turn genes on and off, or to ‘dim’ their activity. Around 75 million (one in ten) of the Cs in the human genome are methylated.

Now, researchers at the Wellcome Trust-Cancer Research UK Gurdon Institute and the Medical Research Council Cancer Unit at the ̽��ֱ�� of Cambridge have identified and characterised a new form of direct modification – methylation of the base A – in several species, including frogs, mouse and humans.

Methylation of A appears to be far less common that C methylation, occurring on around 1,700 As in the genome, but is spread across the entire genome. However, it does not appear to occur on sections of our genes known as exons, which provide the code for proteins.

“These newly-discovered modifiers only seem to appear in low abundance across the genome, but that does not necessarily mean they are unimportant,” says Dr Magdalena Koziol from the Gurdon Institute. “At the moment, we don’t know exactly what they actually do, but it could be that even in small numbers they have a big impact on our DNA, gene regulation and ultimately human health.”

More than two years ago, Dr Koziol made the discovery while studying modifications of RNA. There are 66 known RNA modifications in the cells of complex organisms. Using an antibody that identifies a specific RNA modification, Dr Koziol looked to see if the analogous modification was also present on DNA, and discovered that this was indeed the case. Researchers at the MRC Cancer Unit then confirmed that this modification was to DNA, rather than from any RNA contaminating the sample.

“It’s possible that we struck lucky with this modifier,” says Dr Koziol, “but we believe it is more likely that there are many more modifications that directly regulate our DNA. This could open up the field of epigenetics.”

̽��ֱ��research was funded by the Biotechnology and Biological Sciences Research Council, Human Frontier Science Program, Isaac Newton Trust, Wellcome Trust, Cancer Research UK and the Medical Research Council.

Reference
Koziol, MJ et al. Identification of methylated deoxyadenosines in vertebrates reveals diversity in DNA modifications. Nature Structural and Molecular Biology; 21 Dec 2015

̽��ֱ��world of epigenetics – where molecular ‘switches’ attached to DNA turn genes on and off – has just got bigger with the discovery by a team of scientists from the ̽��ֱ�� of Cambridge of a new type of epigenetic modification.

It’s possible that we struck lucky with this modifier, but we believe it is more likely that there are many more modifications that directly regulate our DNA

Magdalena Koziol

Wokandapix

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̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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How the stick insect sticks (and unsticks) itself

jeh98 — Wed, 07 Oct 2015 13:12:35 +0000

Geckos, tree frogs, spiders and insects all share a special skill – they can walk up vertical surfaces and even upside down using adhesive pads on their feet. But geckos have ‘dry’ feet, while insects have ‘wet’ feet.

Scientists have assumed that the two groups use different mechanisms to keep their feet firmly attached to a surface, but new research from David Labonte and Dr Walter Federle in the ̽��ֱ�� of Cambridge’s Department of Zoology provides evidence that this isn’t actually the case.

“It has generally been assumed that the fluid on their feet must be involved in helping insects like stick insects adhere to a surface by capillary and viscous forces – in the same way that a beer glass will stick to a glass table if it’s wet on the bottom,” explains Labonte, lead author of the study published in Soft Matter, “but our research shows that the fluid is likely used for something else entirely – it may even help insects unstick their feet.”

By measuring how much force was required to detach the foot of a stick insect from a glass plate at different speeds and applying the theory of fracture mechanics, Labonte and Federle found that only a ‘dry’ contact model could explain the data. They also carried out a comparison of the sticking performance of wet and dry adhesive pads, which revealed that there is a striking lack of differences between the two, contrary to previous opinion.

Insects and geckos need to walk up vertical surfaces and even upside down in order to get to the places where they feed and to escape from predators. As smooth surfaces don’t allow them to grip with their claws, they need soft adhesive pads on their feet and legs. This means they need to have excellent control over adhesion – to ensure their feet stick when they want them to, but can also unstick easily to allow them to walk around or run away from predators.

“Both wet and dry adhesive pads behave in a similar way to soft, rubbery materials in that, when they are pressed against another surface, there is a large area of contact between the two surfaces,” says Labonte. Both pad types then rely on shear forces to control their stickiness: insect and gecko feet are much stickier when they are pulled towards the body.

“ ̽��ֱ��fluid that insects have on their adhesive pads doesn’t seem to increase the pads' stickiness by means of capillary or viscous forces, and the same may hold for the fluid on the feet of spiders and tree frogs.”

So what is this fluid for?

Labonte and Federle believe it may act as a ‘release layer’ to help insects unstick their feet when they want to move. “If you think of commercial adhesives, like Scotch tape, there are often bits of tape or residue left behind when you remove it quickly. But a stick insect needs to be able to unstick its feet without expending a lot of energy or leaving bits of its foot still stuck to a leaf,” explains Federle.

“ ̽��ֱ��fluid may act as a lubricant to make detachment easier, giving insects greater control over adhesion at very short timescales.”

“When the first microscopes were invented in the 17th century, one of the first things scientists looked at was a fly’s foot. ̽��ֱ��purpose of the fluid that you find on insects’ feet has remained a fascinating question ever since,” says Labonte.

But it’s not just an age-old question that this research is helping to answer. ̽��ֱ��researchers say there may be lessons to learn for modern manmade devices.

“Understanding how insects control adhesion could have applications where adhesion is needed in a dynamic context, for instance in the production of small electronic devices, where it’s necessary to pick up and place down tiny parts with ease and accuracy,” adds Federle.

This research was enabled by funding from the Biotechnology and Biological Sciences Research Council and the Human Frontier Science Programme.

Reference:

David Labonte and Walter Federle ‘Rate-dependence of ‘wet’ biological adhesives and the function of the pad secretion in insects’ Soft Matter (2015).

Inset images: Composite figure showing the adhesive pad on the foot of a stick insect (T Endlein and David Labonte); Stick insect (T Endlein); Ant's foot showing a fluid trail (Walter Federle).

New research shows the fluid found on insects’ feet does not help them adhere to vertical and inverted surfaces, as previously thought, but may in fact help them to unstick their feet more easily to allow greater control over their sticking power.

When the first microscopes were invented in the 17th century, one of the first things scientists looked at was a fly’s foot. ̽��ֱ��purpose of the fluid that you find on insects’ feet has remained a fascinating question ever since

David Labonte

Walter Federle

Ant's foot showing a fluid trail

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

̽��ֱ�� of Cambridge - Human Frontier Science Programme

Epigenetic discovery suggests DNA modifications more diverse than previously thought

How the stick insect sticks (and unsticks) itself