(Press-News.org) CAMBRIDGE, Mass. (October 10, 2013) – Having recently discovered a set of powerful gene regulators that control cell identity in a few mouse and human cell types, Whitehead Institute scientists are now showing that these regulators—which they named "super-enhancers"—act across a vast array of human cell types and are enriched in mutated regions of the genome that are closely associated with a broad spectrum of diseases.
The findings, published online today by the journal Cell, suggest that these super-enhancers, first described in Cell several months ago by Whitehead Member Richard Young, could ultimately play important roles in disease diagnostics and therapeutics.
In April, Young reported that while the total number of genetic control elements is likely in the millions, only a few hundred super-enhancers regulate the key genes that give each cell its unique properties and functions. At the time, Young hinted that the discovery, which was based on work primarily in embryonic stem cells, would help to solve the regulatory circuitry of all human cells. This latest research represents a significant step toward that goal, producing a catalog of super-enhancers in nearly 100 human cell and tissue types.
"We've gone from a few cells to a broad swath of human cell types to create this resource and make it available to the biomedical research community," says Young, who is also a professor of biology at MIT.
Young notes that the striking finding of the new study is that beyond their roles in control of healthy cells, super-enhancers are involved in regulating the function—and dysfunction—of diseased cells.
"We were surprised that for so many different diseases, mutations associated with the disease occur in super-enhancers" says postdoctoral scientist Brian Abraham, an author of the study. Indeed, he and other researchers in Young's lab found in disease-relevant cell types genetic mutations associated with Alzheimer's disease, diabetes, and many autoimmune diseases in genomic regions under the control of specific super-enhancers.
The researchers also found super-enhancers operating in particularly insidious fashion across a broad spectrum of cancers, observing cancer cells assembling their own super-enhancers to overproduce malevolent oncogenes that drive such cancer hallmarks as hyperproliferation, invasion, and metastasis. Young believes that identifying, mapping, and disrupting super-enhancers could alter the way cancers are managed in the clinic.
"When we focus on personalized medicine for cancer patients, super-enhancers could serve as useful biomarkers for tracking and understanding the evolution of a person's cancer," says Young. "Ultimately, super-enhancers may well become important targets for therapeutic intervention."
This work was supported by grants from the National Institutes of Health (grants HG002668, CA109901, and CA146445).
###
Richard Young's primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a professor of biology at Massachusetts Institute of Technology.
Full Citations:
"Super-enhancers in the control of cell identity and disease"
Cell, online, October 10, 2013
Denes Hnisz (1), Brian J. Abraham (1), Tong Ihn Lee (1), Ashley Lau (1,2), Violaine Saint-André (1), Alla A. Sigova (1), Heather Hoke (1,2), Richard A. Young (1,2)
1. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142
2. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139
END
A new study by a University of British Columbia researcher finds that some people are genetically predisposed to see the world darkly.
The study, published in Psychological Science, finds that a previously known gene variant can cause individuals to perceive emotional events—especially negative ones – more vividly than others.
"This is the first study to find that this genetic variation can significantly affect how people see and experience the world," says Prof. Rebecca Todd of UBC's Dept. of Psychology. "The findings suggest people experience emotional aspects of ...
LA JOLLA, CA -- October 9, 2013 -- A team led by scientists at The Scripps Research Institute (TSRI) has identified key signaling proteins in the inflammation process that contribute to the development of inflammatory diseases such as rheumatoid arthritis, psoriasis, sepsis and inflammatory bowel diseases. The finding highlights possible new ways of treating these inflammation disorders, which sicken or kill millions of people around the world each year.
"We hope our approach will lead to the development of drugs that augment current anti-inflammatory strategies," said ...
This new method will be a great step forwards to understanding the resulting processes that control gene regulation.
These results were published on October 6, 2013 on the website of the review Nature Structural & Molecular Biology.
In the cell nucleus, DNA is highly dynamic and changes its spatial configuration, in the same way as during the process of cell division. We already know that the spatial configuration of DNA determines whether the genes are active or inactive, in other words whether they are capable of expression. In this study, the researchers attempted ...
When we are sad the world seemingly cries with us. On the contrary, when we are happy everything shines and all around people's faces seem to rejoyce with us. These projection mechanisms of one's emotions onto others are well known to scientists, who believe they are at the core of the ability to interpret and relate to others. In some circumstances, however, this may lead to gross mistakes (called egocentricity bias in the emotional domain EEB), to avoid them cerebral mechanisms are activated about which still little is known.
Giorgia Silani, a neuroscientist at SISSA, ...
Bariatric surgeries, such as a gastric bypass, are currently the most effective anti-obesity therapies. They also lead to a reduced insulin resistance. However, the pitfall of these surgical interventions is that they are highly invasive and often permanent procedures. An international team of scientists led by Dr. Kirk Habegger, Metabolic Disease Institute, University of Cincinnati, and Prof. Dr. Matthias Tschöp, Scientific Director of the Helmholtz Diabetes Center (HDC) at the Helmholtz Zentrum München (HMGU), Partner of the German Center for Diabetes Research (DZD), ...
This work, published on 10th October on the website of Nature Communications, concerns the role of one protein which is common to these parasites. Called AMA1, it has been at the heart of many years' research on upgrading treatments, such as trying out vaccination against malaria. However, the present authors have reservations about the success of therapeutic strategies which rely solely on the blockage of AMA1, by demonstrating that the malaria and toxoplasmosis parasites, without the protein, can develop normally.
With 1 million victims every year, malaria is the most ...
This news release is available in German. Egoism and narcissism appear to be on the rise in our society, while empathy is on the decline. And yet, the ability to put ourselves in other people's shoes is extremely important for our coexistence. A research team headed by Tania Singer from the Max Planck Institute for Human Cognitive and Brain Sciences has discovered that our own feelings can distort our capacity for empathy. This emotionally driven egocentricity is recognised and corrected by the brain. When, however, the right supramarginal gyrus doesn't function properly ...
Rice University scientists took a lesson from craftsmen of old to assemble microscopic compounds that warn of the presence of dangerous fumes from solvents.
The researchers combined a common mineral, zeolite, with a metallic compound based on rhenium to make an "artificial nose" that can sniff out solvent gases. They found that in the presence of the compound, each gas had a photoluminescent "fingerprint" with a specific intensity, lifetime and color.
Rice chemist Angel Martí and his students reported their results this month in the journal Angewandte Chemie.
The ...
The volcano on the Scottish peninsula Ardnamurchan is a popular place for the study of rocks and structures in the core of a volcano. Geology students read about it in text books and geologists have been certain that the Ardnamurchan volcano have three successive magma chambers. However, an international group of researchers, lead from Uppsala University, Sweden, has now showed that the volcano only has one single magma chamber.
The new study is published in Scientific Reports, the new open access journal of the Nature Publishing Group.
The 58 million year old Ardnamurchan ...
A new study by KU Leuven-iMinds researchers has uncovered that 145 of the Internet's 10,000 top websites track users without their knowledge or consent. The websites use hidden scripts to extract a device fingerprint from users' browsers. Device fingerprinting circumvents legal restrictions imposed on the use of cookies and ignores the Do Not Track HTTP header. The findings suggest that secret tracking is more widespread than previously thought.
Device fingerprinting, also known as browser fingerprinting, is the practice of collecting properties of PCs, smartphones and ...
