Breaking News
May 3, 2019 - Vaping and Smoking May Signal Greater Motivation to Quit
May 3, 2019 - Dementia looks different in brains of Hispanics
May 3, 2019 - Short-Staffed Nursing Homes See Drop In Medicare Ratings
May 3, 2019 - Study of teens with eating disorders explores how substance users differ from non-substance users
May 3, 2019 - Scientists develop new video game that may help in the study of Alzheimer’s
May 3, 2019 - Arc Bio introduces Galileo Pathogen Solution product line at ASM Clinical Virology Symposium
May 3, 2019 - Cornell University study uncovers relationship between starch digestion gene and gut bacteria
May 3, 2019 - How to Safely Use Glucose Meters and Test Strips for Diabetes
May 3, 2019 - Anti-inflammatory drugs ineffective for prevention of Alzheimer’s disease
May 3, 2019 - Study tracks Pennsylvania’s oil and gas waste-disposal practices
May 3, 2019 - Creating a better radiation diagnostic test for astronauts
May 3, 2019 - Vegans are often deficient in these four nutrients
May 3, 2019 - PPDC announces seed grants to develop medical devices for children
May 3, 2019 - Study maps out the frequency and impact of water polo head injuries
May 3, 2019 - Research on Reddit identifies risks associated with unproven treatments for opioid addiction
May 3, 2019 - Good smells may help ease tobacco cravings
May 3, 2019 - Medical financial hardship found to be very common among people in the United States
May 3, 2019 - Researchers develop multimodal system for personalized post-stroke rehabilitation
May 3, 2019 - Study shows significant mortality benefit with CABG over percutaneous coronary intervention
May 3, 2019 - Will gene-editing of human embryos ever be justifiable?
May 3, 2019 - FDA Approves Dengvaxia (dengue vaccine) for the Prevention of Dengue Disease in Endemic Regions
May 3, 2019 - Why Tonsillitis Keeps Coming Back
May 3, 2019 - Fighting the opioid epidemic with data
May 3, 2019 - Maggot sausages may soon be a reality
May 3, 2019 - Deletion of ATDC gene prevents development of pancreatic cancer in mice
May 2, 2019 - Targeted Therapy Promising for Rare Hematologic Cancer
May 2, 2019 - Alzheimer’s disease is a ‘double-prion disorder,’ study shows
May 2, 2019 - Reservoir bugs: How one bacterial menace makes its home in the human stomach
May 2, 2019 - Clinical, Admin Staff From Cardiology Get Sneak Peek at Epic
May 2, 2019 - Depression increases hospital use and mortality in children
May 2, 2019 - Vicon and NOC support CURE International to create first gait lab in Ethiopia
May 2, 2019 - Researchers use 3D printer to make paper organs
May 2, 2019 - Viral infection in utero associated with behavioral abnormalities in offspring
May 2, 2019 - U.S. Teen Opioid Deaths Soaring
May 2, 2019 - Opioid distribution data should be public
May 2, 2019 - In the Spotlight: “I’m learning every single day”
May 2, 2019 - 2019 Schaefer Scholars Announced
May 2, 2019 - Podcast: KHN’s ‘What The Health?’ Bye-Bye, ACA, And Hello ‘Medicare-For-All’?
May 2, 2019 - Study describes new viral molecular evasion mechanism used by cytomegalovirus
May 2, 2019 - SLU study suggests a more equitable way for Medicare reimbursement
May 2, 2019 - Scientists discover first gene involved in lower urinary tract obstruction
May 2, 2019 - Researchers identify 34 genes associated with increased risk of ovarian cancer
May 2, 2019 - Many low-income infants receive formula in the first few days of life, finds study
May 2, 2019 - Global study finds high success rate for hip and knee replacements
May 2, 2019 - Taking depression seriously: What is it?
May 2, 2019 - With Head Injuries Mounting, Will Cities Put Their Feet Down On E-Scooters?
May 2, 2019 - Scientists develop small fluorophores for tracking metabolites in living cells
May 2, 2019 - Study casts new light into how mothers’ and babies’ genes influence birth weight
May 2, 2019 - Researchers uncover new brain mechanisms regulating body weight
May 2, 2019 - Organ-on-chip systems offered to Asia-Pacific regions by Sydney’s AXT
May 2, 2019 - Adoption of new rules drops readmission penalties against safety net hospitals
May 2, 2019 - Kids and teens who consume zero-calorie sweetened beverages do not save calories
May 2, 2019 - Improved procedure for cancer-related erectile dysfunction
May 2, 2019 - Hormone may improve social behavior in autism
May 2, 2019 - Alzheimer’s disease may be caused by infectious proteins called prions
May 2, 2019 - Even Doctors Can’t Navigate Our ‘Broken Health Care System’
May 2, 2019 - Study looks at the impact on criminal persistence of head injuries
May 2, 2019 - Honey ‘as high in sugars as table sugar’
May 2, 2019 - Innovations to U.S. food system could help consumers in choosing healthy foods
May 2, 2019 - FDA Approves Mavyret (glecaprevir and pibrentasvir) as First Treatment for All Genotypes of Hepatitis C in Pediatric Patients
May 2, 2019 - Women underreport prevalence and intensity of their own snoring
May 2, 2019 - Concussion summit focuses on science behind brain injury
May 2, 2019 - Booker’s Argument For Environmental Justice Stays Within The Lines
May 2, 2019 - Cornell research explains increased metastatic cancer risk in diabetics
May 2, 2019 - Mount Sinai study provides fresh insights into cellular pathways that cause cancer
May 2, 2019 - Researchers to study link between prenatal pesticide exposures and childhood ADHD
May 2, 2019 - CoGEN Congress 2019: Speakers’ overviews
May 2, 2019 - A new strategy for managing diabetic macular edema in people with good vision
May 2, 2019 - Sagent Pharmaceuticals Issues Voluntary Nationwide Recall of Ketorolac Tromethamine Injection, USP, 60mg/2mL (30mg per mL) Due to Lack of Sterility Assurance
May 2, 2019 - Screen time associated with behavioral problems in preschoolers
May 2, 2019 - Hormone reduces social impairment in kids with autism | News Center
May 2, 2019 - Researchers synthesize peroxidase-mimicking nanozyme with low cost and superior catalytic activity
May 2, 2019 - Study results of a potential drug to treat Type 2 diabetes in children announced
May 2, 2019 - Multigene test helps doctors to make effective treatment decisions for breast cancer patients
May 2, 2019 - UNC School of Medicine initiative providing unique care to dementia patients
May 2, 2019 - Nestlé Health Science and VHP join forces to launch innovative COPES program for cancer patients
May 2, 2019 - Study examines how our brain generates consciousness and loses it during anesthesia
May 2, 2019 - Transition Support Program May Aid Young Adults With Type 1 Diabetes
May 2, 2019 - Study shows how neutrophils exacerbate atherosclerosis by inducing smooth muscle-cell death
May 2, 2019 - Research reveals complexity of how we make decisions
Study identifies link between DNA-protein binding, cancer onset | News Center

Study identifies link between DNA-protein binding, cancer onset | News Center

Researchers at the Stanford University School of Medicine and their collaborators at other institutions have identified a link between how proteins bind to our DNA and how cancer develops. This finding may allow researchers to predict cancer pathways and long-term patient outcomes.

The research focuses on chromatin, the DNA-protein complex where all genes reside. Specifically, it evaluates chromatin’s relationship to transcription factors — proteins that play a crucial role in managing which genes are activated within cells. Certain genes are turned on or off based on how transcription factors bind to specific parts of the chromatin. The study found that these binding patterns and the resulting gene activation act like a key to different cancer typesallowing the researchers to understand the biology of cancer at its most basic level. 

A paper detailing the research was published Oct. 26 in Science. The senior authors are Howard Chang, MD, PhD, professor of dermatology and of genetics, and William Greenleaf, PhD, associate professor of genetics. Postdoctoral scholar Ryan Corces, PhD, and graduate student Jeffrey Granja share lead authorship. 

Cancer causes a massive burden on society and is among the leading causes of death worldwide. According to the National Cancer Institute, there will be more than 1.7 million new cancer cases by the end of 2018 in the United States. Our total health care expenditures for cancer care in 2014 alone was $87.8 billion — a number that continues to increase as the years go by.

However, diseases that once seemed intractable now have functional treatments, said Chang, who is also the Virginia and D.K. Ludwig Professor of Cancer Genomics. “So, with continued work, cancer is something we can actually make sense of,” he added.

A disease of genes gone awry

Corces said that cancer is “a disease of genes gone awry.” But in order to understand where these harmful genes come from, the researchers had to look inside the nucleus to the cell’s transcription process.     

Transcription occurs when the cell takes information encoded in a gene and rewrites it in the form of messenger RNA. The DNA within a cell’s nucleus is tightly wound together with certain proteins into a threadlike structure known as chromatin, and that chromatin is further coiled to form a larger structure called a chromosome. Because of this coiling, only certain areas of the chromatin sequence are accessible to the cell’s transcription machinery. When a transcription factor finds an available section of chromatin and binds to it, that region of the DNA sequence unzips, allowing transcription to occur. However, in the case of cancer, the transcription process malfunctions, resulting in a change in gene activation.   

These switches that determine gene activity were our missing component.

To understand exactly what goes wrong during this critical stage, the researchers used 410 tumor samples, representing 23 different cancer types, from The Cancer Genome Atlas and a newly developed technique called assay for transposase-accessible chromatin using sequencing, or ATAC-seq. As Chang explained, ATAC-seq is like spray-painting your DNA but only the accessible chromatin gets painted, giving researchers a fast and easy way to identify key protein-binding areas.  

One finding showed that mutations can occur within the chromatin sequence, thereby creating a new and accessible site where a transcription factor can bind. Once the protein attaches to the site, a new gene is expressed, causing significant biological changes. 

An example of this occurred with bladder cancer tissue that the researchers examined. When the team performed ATAC-seq on the tissue, they noticed that a chromatin mutation created a new protein-binding site that was associated with a strong increase in the activity of a neighboring genethat regulates cell size, motility and shape — all of which are classic factors in cancer growth. Even more interesting was that this particular mutation was not present in the other cancer tissues analyzed in the study, suggesting that different cancer types may arise from different chromatin mutations.   

“These switches that determine gene activity were our missing component,” Chang said. “We can now find how these switches are changing cancer, including mutations that make the switch get stuck in the on position.” 

The tip of the iceberg

The vast amount of genetic research is focused on the 2 percent of our DNA that is used to create proteins. In the current study, Chang wanted to explore the other 98 percent. Called the “noncoding” section, this part of our DNA is used to make crucial regulatory components that control gene behavior and activation. It also includes information that is pertinent to cancer.   

Through this work, Chang hopes to open the door to understanding the breadth of the human genome, and of cancer itself. Moving forward, the team expects far more research aimed at discovering and understanding the effects of these noncoding sequences. 

Although the team’s findings have yet to be applied in a clinical setting, the researchers believe their work will be useful in the development of better cancer prognoses, more information on patient susceptibility to cancer and new treatments that are more localized and effective.   

Beyond its potential clinical impact, Corces said he believes the research provides valuable knowledge about cancer gene regulation.“Other people are undoubtedly going to use this chromatin accessibility data to further understand how networks of genes effect cancer,” he said. 

Other Stanford co-authors of the paper are postdoctoral scholar Seung Woo Cho, PhD; graduate student Maxwell Mumbach; research associate Shadi Shams; technician Bryan Louie; research scientists Jose Seoane, PhD, and Ansuman Satpathy, PhD; and assistant professor Christina Curtis, PhD. 

Researchers from several other institutions were co-authors of the work and are listed in the paper.

Chang is a Howard Hughes Medical Institute investigator, and Greenleaf is a Chan-Zuckerberg Biohub investigator. They are both members of Stanford Bio-X, the Stanford Cancer Institute, the Stanford Neurosciences Instituteand the Stanford Child Health Research Institute

The research was supported by the National Institutes of Health (grants R35Ca209919, P50HG007735, K99AG059918, 1U24CA210974, 1U24CA210949, 1U24CA210978, 1U24CA210952, 1U24CA210989, 1U24CA210990, 1U24CA210950, 1U24CA210969 and 1U24CA210988) and the Parker Institute for Cancer Immunotherapy.

Stanford’s departments of Genetics and of Dermatology also supported this work.

Tagged with:

About author

Related Articles