Nav: Home

Reader of epigenetic marks could be 'game changer' for certain cancers

April 18, 2016

If genes form the body's blueprint, then the layer of epigenetics decides which parts of the plan get built. Unfortunately, many cancers hijack epigenetics to modulate the expression of genes, thus promoting cancer growth and survival. A team of researchers led by Tatiana Kutateladze, PhD, University of Colorado Cancer Center investigator and professor in the Department of Pharmacology at the University of Colorado School of Medicine, and Brian Strahl, PhD, professor in the Department of Biochemistry & Biophysics at the University of North Carolina School of Medicine, published a breakthrough report in the journal Nature Chemical Biology describing the essential role of YEATS domain proteins in reading epigenetic marks that regulate gene expression, DNA damage response, and other vital DNA-dependent cellular processes. This newly discovered player in epigenetic regulation is closely related to known cancer promoters, including the bromodomain proteins, a handful of which are targeted in current human clinical trials.

"Every cell in an organism has the same DNA. So how does a heart cell become a heart cell and a skin cell become a skin cell? There's a language called epigenetics that helps determine which genes are turned on and turned off at any given moment," says Forest Andrews, PhD, a postdoctoral fellow in Kutateladze's laboratory and, together with Stephen Shinsky, PhD, a postdoctoral fellow in Strahl's laboratory, a co-first author on the paper.

Epigenetic mechanisms control how often a gene's blueprint ultimately yields a protein, modulating the structure and dynamics of chromatin, a complex consisting of DNA and histone proteins. The addition or removal of epigenetic marks on histone proteins is one of such mechanisms that helps expose some regions of DNA to promote gene expression, while keeping other regions of DNA hidden inside the chromatin fiber.

The study by Andrews et al. has uncovered the YEATS domain as the first reader of histone lysine crotonylation, a critical epigenetic mark, which was discovered only recently and is strongly linked to the initiation of protein production. The authors found that the yeast YEATS protein recognizes this epigenetic mark through a unique mechanism that has not been previously reported for any protein-protein interaction. This fundamental basic science discovery also has compelling implications for human disease and could be a potential game-changer for some cancers as two human YEATS proteins have been implicated in leukemia and another is dysregulated in glioblastoma.

Furthermore, the YEATS proteins are closely related to bromodomain proteins, which Andrews calls "a hot target for cancer drugs". In fact, Andrews and Kutateladze teamed up with the group of Donald Durden, MD, PhD, professor in the Department of Pediatrics at the University of California San Diego (UCSD) and associate director of Pediatric Oncology at the Moores UCSD Cancer Center, to develop novel dual activity bromodomain/kinase inhibitors that target epigenetic and PI3K signaling pathways. This work is presented at the American Association for Cancer Research 2016 Annual Meeting.

Mechanisms of the epigenetic regulation are at the focus of research in Kutateladze's laboratory. "We hope these discoveries open up new opportunities and strategies to diagnose, prevent or treat cancer," says Kutateladze.
-end-


University of Colorado Anschutz Medical Campus

Related Dna Articles:

Scientists now know what DNA's chaperone looks like
Researchers have discovered the structure of the FACT protein -- a mysterious protein central to the functioning of DNA.
In one direction or the other: That is how DNA is unwound
DNA is like a book, it needs to be opened to be read.
DNA is like everything else: it's not what you have, but how you use it
A new paradigm for reading out genetic information in DNA is described by Dr.
A new spin on DNA
For decades, researchers have chased ways to study biological machines.
From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.
Self-healing DNA nanostructures
DNA assembled into nanostructures such as tubes and origami-inspired shapes could someday find applications ranging from DNA computers to nanomedicine.
DNA design that anyone can do
Researchers at MIT and Arizona State University have designed a computer program that allows users to translate any free-form drawing into a two-dimensional, nanoscale structure made of DNA.
DNA find
A Queensland University of Technology-led collaboration with University of Adelaide reveals that Australia's pint-sized banded hare-wallaby is the closest living relative of the giant short-faced kangaroos which roamed the continent for millions of years, but died out about 40,000 years ago.
DNA structure impacts rate and accuracy of DNA synthesis
DNA sequences with the potential to form unusual conformations, which are frequently associated with cancer and neurological diseases, can in fact slow down or speed up the DNA synthesis process and cause more or fewer sequencing errors.
Changes in mitochondrial DNA control how nuclear DNA mutations are expressed in cardiomyopathy
Differences in the DNA within the mitochondria, the energy-producing structures within cells, can determine the severity and progression of heart disease caused by a nuclear DNA mutation.
More Dna News and Dna Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Accessing Better Health
Essential health care is a right, not a privilege ... or is it? This hour, TED speakers explore how we can give everyone access to a healthier way of life, despite who you are or where you live. Guests include physician Raj Panjabi, former NYC health commissioner Mary Bassett, researcher Michael Hendryx, and neuroscientist Rachel Wurzman.
Now Playing: Science for the People

#544 Prosperity Without Growth
The societies we live in are organised around growth, objects, and driving forward a constantly expanding economy as benchmarks of success and prosperity. But this growing consumption at all costs is at odds with our understanding of what our planet can support. How do we lower the environmental impact of economic activity? How do we redefine success and prosperity separate from GDP, which politicians and governments have focused on for decades? We speak with ecological economist Tim Jackson, Professor of Sustainable Development at the University of Surrey, Director of the Centre for the Understanding of Sustainable Propserity, and author of...
Now Playing: Radiolab

An Announcement from Radiolab