Navigation Links
Study uncovers clues to cystic fibrosis gene dysfunction and gastrointestinal disease

PROVIDENCE, R.I. A new study by researchers at Hasbro Childrens Hospital, the pediatric division of Rhode Island Hospital, and Mount Sinai Hospital, New York, offers new insight into the role that the cystic fibrosis gene plays in the development of gastrointestinal disease.

The cystic fibrosis transmembrane conductance regulator (CFTR) gene codes for a protein also known as CFTR. Mutations of this protein are associated with cystic fibrosis (CF) and a range of digestive diseases, such as inflammation of the pancreas, that can be severe and debilitating and can occur even in patients without CF. Yet the underlying mechanism by which CFTR gene dysfunction causes disease is poorly understood, limiting potential treatment options.

In the December 15th issue of the Biochemical Journal, scientists report the discovery of a new regulatory element in a region of the CFTR gene that can control the genes expression in the gastrointestinal tract. They also identified three important and active regulatory factors at this site that are known to control major aspects of intestinal cell regulation, including cell differentiation and growth.

We hope that these findings will lead to a more comprehensive understanding of how CFTR gene dysfunction can cause such a wide range of disease, eventually enabling us to develop effective treatments for cystic fibrosis and other gastrointestinal diseases, said lead author Thankam Paul, M.D., a pediatric gastroenterologist at Hasbro Childrens Hospital and assistant professor of pediatrics at The Warren Alpert Medical School of Brown University.

The CFTR protein resides in the surface of cells lining the digestive system, lungs and sweat glands. In normal cells, it acts as an ion channel that transports chloride into and out of cells. It also controls the regulation of other transport pathways regulating the passage of fluid and bicarbonate across cell membranes.

Previous research indicates that DNA sequence variations (or mutations) alone do not explain CFTR-related gastrointestinal disease patterns; rather, epigenetic modifiers, or changes that leave the genes sequence of DNA intact, influence CFTR expression.

Paul and colleagues sought to define regions within the CFTR gene that correlate with histone acetylation, a process that modifies DNA-packaging proteins. After identifying a region associated with acute acetylation of histone H4, one of the major core histones, they conducted further tests which linked this process to active intestinal CFTR expression and occupation by regulatory factors known as HNF1a, Cdx2 and Tcf4. The combined activity of these factors appears to modify the architecture of chromatin, the form in which DNA is packaged in the cell, leading to alterations of CFTR expression.

Our findings suggest the therapeutic potential of histone modification strategies to treat CFTR-associated disease by selectively enhancing CFTR expression, said Neal LeLeiko, M.D., Ph.D., study co-author and director of the division of gastroenterology, nutrition and liver diseases at Hasbro Childrens Hospital. He is also a professor of pediatrics at Alpert Medical School.


Contact: Jessica Collins Grimes

Related biology news :

1. Childhood obesity indicates greater risk of school absenteeism, Penn study reveals
2. A study by the MUHC and McGill University opens a new door to understanding cancer
3. Study begins to reveal clues to the cause and progression of sepsis
4. Clones on task serve greater good, evolutionary study shows
5. New study warns limited carbon market puts 20 percent of tropical forest at risk
6. New study examines how rearing environment can alter navigation
7. Study links cat disease to flame retardants in furniture and to pet food
8. New continent and species discovered in Atlantic study
9. Study shows link between alcohol consumption and hiv disease progression
10. Feeling hot, hot, hot: New study suggests ways to control fever-induced seizures
11. Study finds environmental tests help predict hospital-acquired Legionnaires disease risk
Post Your Comments:
(Date:10/29/2015)... 2015  Rubicon Genomics, Inc., today announced an ... its DNA library preparation products, including the ThruPLEX ... Plasma-seq kit. ThruPLEX Plasma-seq has been optimized for ... libraries for liquid biopsies--the analysis of cell-free circulating ... in cancer and other conditions. Eurofins Scientific is ...
(Date:10/27/2015)... Munich, Germany , ... (ASGM) automatically maps data from mobile eye tracking videos ... so that they can be quantitatively analyzed with SMI,s ... Germany , October 28-29, 2015. SMI,s Automated Semantic ... eye tracking videos created with SMI,s Eye Tracking ...
(Date:10/23/2015)... 23, 2015 Research and Markets ( ... Voice Recognition Biometrics Market 2015-2019" report to their ... The global voice recognition biometrics market to grow ... --> --> The report, ... based on an in-depth market analysis with inputs from ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... ... 2015 , ... The United States Golf Association (USGA) today announced Dr. Bruce ... Presented annually since 1961, the USGA Green Section Award recognizes an individual’s distinguished service ... , Clarke, of Iselin, N.J., is an extension specialist of turfgrass pathology in the ...
(Date:11/24/2015)... Tampa, Florida (PRWEB) , ... November 24, 2015 ... ... its biggest event of the year and one of the premier annual events ... USA, and ran from 8–11 November 2015, where ISPE hosted the largest number ...
(Date:11/24/2015)... ... ... The Academy of Model Aeronautics (AMA), led by its Executive Council, has officially ... to represent the First–Person View (FPV) racing community. , FPV racing has exploded in ... racing and several new model aviation pilots have joined the community because of their ...
(Date:11/24/2015)... 24, 2015  Twist Bioscience, a company focused ... Ph.D., Twist Bioscience chief executive officer, will present ... December 1, 2015 at 3:10 p.m. Eastern Time at The ... --> --> ... Bioscience is on Twitter. Sign up to follow ...
Breaking Biology Technology: