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A brief look at the epigenetics research stories that caught our eye this year.
Post-traumatic stress disorder (PTSD) can be triggered by exposure to a traumatic event, causing flashbacks and anxiety in sufferers. Research published by Johannes Gräff and colleagues suggests that treatment with histone deacetylase inhibitors may make the brain more amenable to extinction therapy; a form of therapy that often has only limited success.
When a patient recalls a traumatic memory in a safe environment during extinction therapy, the memory becomes amenable to change in a process called reconsolidation. Over time, new memories replace the old, traumatic memory. However, if a memory is too old, it becomes resistant to reconsolidation, meaning that traumatic memories can haunt PTSD sufferers for a lifetime.
The work showed that histone acetylation increased in the brain during the reconsolidation update stage; this is when recent memories are most vulnerable to modification. During this period, histone deacetylase 2 (HDAC2) dissociated from chromatin.
When researchers treated mice displaying remote fear memories with a HDAC2 inhibitor, they found that remote memories were reconsolidated as effectively as recent memories.
This research raises the possibility that the use of HDAC2 inhibitors in combination with extinction therapy may one day be used as an effective PTSD therapy. Such a breakthrough would revolutionize the treatment of this condition.
In April, we got to find out a little more about our closest evolutionary relatives. A team lead by Liran Carmel from the Hebrew University of Jerusalem revealed the epigenome of a 30,000 year old Neanderthal, in a piece of research published in Science.
The epigenome showed that a cluster of genes important for limb development, HOXD genes, were differentially methylated between Neanderthals and modern humans. These results suggest that differences in the epigenomes of modern humans and Neanderthals may have led to our anatomical differences.
Sequencing of the Neanderthal genome had previously shown the genomes of modern and archaic humans to be remarkably similar. This new research provides a potential explanation for how our DNA sequences are so similar, yet our physical traits so different.
Whether or not epigenetic changes can be passed between generations and how long they continue to have an impact has continued to be a focus for debate throughout 2014. In July, some light was shed on these questions in a study published in Science.
By looking at two generations of mice descended from an undernourished mother, Elizabeth Radford, Anne Ferguson-Smith and colleagues found that the offspring and grandchildren of the undernourished mice were smaller than normal and more prone to diabetes.
Probing further, they discovered that this trait was passed down the paternal line via epigenetic changes. The sperm of male offspring had decreased methylation across numerous stretches of DNA, in particular near genes involved in metabolism. Differential methylation in sperm led to changes in gene expression in the next generation.
Although the grandchildren of the undernourished female had altered gene expression, the researchers found that their DNA did not carry the changes in DNA methylation present in their father's sperm. So, while DNA methylation might be important for gene expression in the offspring, these epigenetic marks do not persist through multiple generations.
In August, Katie Lunnon and colleagues from the University of Exeter and King's College London published data supporting a role of epigenetics in Alzheimer's disease.
By analyzing the Alzheimer's disease epigenome of different parts of the brain, they found that neuropathy was strongly associated with changes in DNA methylation in the ankynin 1 (ANK1) gene. Furthermore, differential methylation at ANK1 was pronounced in the entorhinal cortex, a primary site in the brain for Alzheimer's disease manifestation.
These exciting results link ANK1 to Alzheimer's and highlight a potential new mechanism involved in the formation of Alzheimer's disease.
Each month, we summarize key papers from the world of epigenetics as part of our Top Epigenetics articles series.
Throughout 2014, members of the Abcam team have been traveling to conferences all over the globe. Here are some of our favorite conferences that we attended on epigenetics topics, and why we liked them.
"Speakers were uniformly excellent, and the poster sessions equally showed the breadth of research interests and quality of the delegates."
This Wellcome Trust conference focused on variant histones, chromatin domains and their structure and dynamics in living cells. In their keynote talks, Jane Mellor and William Earnshaw shared insights gained from careers spent studying epigenetics and chromatin.
Crossing Boundaries: Linking Metabolism to Epigenetics 2014 | May 1–2 2014, Cambridge, MA.
"I really remember this meeting as one of the most interesting ones I have been to. It brought together the interesting cross section between nutrition and epigenome integrity: the concept of 'you are what you eat'."
This meeting, chaired by Raul Mostoslavsky and Abcam, focused on the crosstalk between metabolic demands and chromatin, and their contribution to cellular homeostasis. The keynote talk was delivered by Craig Thompson.
"I had the chance to attend a Nobel lecture, network with researchers at all levels and get a snapshot of what is going on in epigenetics."
This Abcam meeting was chaired by Maria Elena Torres-Padilla and Robert Schneider. It brought genome-wide approaches together with single cell analysis, with the aim of understanding epigenetic mechanisms in vivo. John Gurdon and Tony Kouzarides delivered keynote presentations.
"This meeting provided a great overview of epigenetics in a range of model organisms. It was great to catch up with collaborators and hear about their unpublished research."
This meeting covered diverse topics in epigenetics such as reprogramming, long-range interactions, DNA and histone modifications, and epigenetic plasticity. A keynote talk was presented by Hans Schöler.
The next big thing in epigenetics
Every month, we interview a scientist who has made a significant contribution to the field of epigenetics. We asked them what they thought the next big breakthrough in epigenetics would be:
"I think the major question is now at what frequency do epigenetic changes occur? Are these changes occurring continuously, or are some of them sufficiently stable that they contribute to the general stability of cell differentiation?"
"Hopefully, in the next few years we will have a better view of the real contributions of epigenetic alterations in a wide range of human diseases, and the possibility of generating specific epigenetic drugs will constitute a major breakthrough."
"Discovering the epigenetic 'substance(s)' that underpin transgenerational effects has been a major challenge and their identification will be transformative for the field. I wait with anticipation to see how these discoveries unfold."
"A future big breakthrough would be single-cell epigenetics in multicellular organisms to unravel not only the dynamic nature of epigenetic changes in normal and diseased state but also the mechanisms behind them."
"One of the major questions to be addressed is that of transgenerational inheritance of modification. This is a very interesting but controversial area of research. It is a difficult but important area to be explored because of its implications with respect to environmental effects over our genetic makeup."
Our pick of the most exciting new epigenetics methods and technologies from this year.
Published in Nature Methods in July, this new method can accurately measure DNA methylation across the whole genome. DNA is first bisulfate treated to convert unmethylated cytosine to thymidine. Treated DNA is then amplified and read by high throughput sequencing. This new approach will enable us to enhance our understanding of embryonic development and may have a role in advancing cancer therapy.
Chromosome conformation capture (3C) and associated methods, including 4C, 5C and Hi-C, have allowed researchers to interrogate the spatial organization of chromatin and chromatin interactions with the genome (for more information, see our 3C guide). However, there are limitations to these techniques, including moderate to low resolution and low throughout with older techniques, or a large, expensive sequencing effort with Hi-C.
However, two new techniques, based on 3C technology, have been published this year that aim to overcome these limitations. Capture-C is a high throughput approach to analyze cis interactions at high resolution on a genome-wide scale. T2C uses selective enrichment of 3C ligation products in regions of interest to produce a high-resolution map for loci of interest.
Our most popular resources
We have a range of resources to help you with your research. Here is a glimpse at some of the articles, protocols and webinars that were popular throughout 2014.