Navigation Links
Protein Packages Found To Activate Genes; May Be What Regulates Development And Disease

It's all in the packaging. How nature wraps and tags genes determines if and when they become active, according to researchers from Harvard and the Massachusetts Institute of Technology (M.I.T.). They did the largest, most detailed study to date of the protein structure that surrounds the human genome.

Their findings reveal surprising and previously unknown specifics of how genes get switched on during development of the human body and in diseases such as cancer.

"Each type of cell in our bodies contains the same genes. What makes them do different things involves which genes are turned on," notes Bradley Bernstein, a pathologist at Harvard Medical School. He is also a research associate at the Broad Institute of Harvard and M.I.T., where a complex analysis of packaging of two entire human chromosomes was done for the first time.

Besides Bernstein, the investigators included Morris Loeb Professor of Chemistry Stuart Schreiber; Michael Kamal, Eric Lander, and others at the Broad Institute; and their colleagues from Affymetrix, a California technology company.

The analysis shows a striking and surprising exception in the way some critical genes are activated by the protein packaging. These proteins act like spools for the long strings of DNA that contain our genes and form chromosomes. The researchers studied chemical tags that are attached to the spools and switch on the genes they wrap. In most cases, they found these tags turn genes on and off individually. The big surprise involves clusters of so-called "HOX" genes, which apparently work in concert to control how we develop in the womb. Instead of being activated individually like most genes, the HOX genes appear to be turned on in groups by massive numbers of tags.

HOX genes also are deeply involved in cancer, making the findings particularly important. Some of the proteins that regulate HOX genes are capable of causing or suppressing tumors.

Technological breakthrou gh

Bernstein has been studying chromosome wrappings for five years as a postdoctoral researcher in the lab of Stuart Schreiber. Together they worked out techniques to examine the way genes are packaged in yeast. To go from yeast to humans required a technological breakthrough, however.

"Most prior studies involved only single genes, but we wanted to investigate entire chromosomes, which contain hundreds of genes," Bernstein notes.

He and Schreiber enlisted the help of Affymetrix, which makes so-called "gene chips" that rapidly scan millions of small sections of chromosomes to detect gene activity. But the scanning results left them with a huge amount of data, and the daunting task of deciphering what it means in terms of how genes function. For that part of the project, they teamed with investigators from the Broad (pronounced to rhyme with "road") Institute.

"The human genome still has many surprises lurking within it," comments Lander, who is director of the institute. "One of the most important is the mystery of how genes are turned on. The ability to take global views of (chromosome packaging) in human cells holds tremendous promise for unraveling the mystery."

To begin unraveling this mystery, the researchers studied large regions of the genome and identified the DNA sequences associated with chromatin that contains "on" tags. DNA is the same in all the cells in our body. What makes the cells do different jobs is that different genes are turned on. For example, the set of genes turned on in a nerve cell is different from those turned on in muscle, heart, blood, and other cells.

Although the exact ways genes are turned on and off remain unknown, the tags in chromatin are believed to play a major role. Until now, however, it had not even been known which regions of the genome carry such tags.

A complete surprise

Most regions of the chromatin have only a few "on" tags, but in regions packaging cluster s of HOX genes hundreds of such tags exist. Yeast cells don't have such clusters, but HOX clusters in mice and humans boast relatively huge sections of chromatin completely covered with tags. This was not seen before by using standard techniques, or by studying one gene at a time. "Finding them was a complete surprise," Bernstein admits.

HOX genes, as noted, play vital roles in embryo development. Understanding how they are regulated should help researchers determine the molecule-by-molecule procedure involved in the assembly of organs and tissues, like brains and muscles, into a complex living organism.

HOX genes are also vital for understanding the way that people get certain cancers. "Many of the proteins that regulate these genes can suppress or enhance tumor growth," Bernstein notes. "Some of the genes can cause cancer directly when altered by mutations."

"The work we're doing now is very fundamental," he says. "But what we learn about the interactions between chromatin, its tags, and various proteins that interact with them may one day be useful for understanding, diagnosing, and even developing new treatments for some cancers."


'"/>

Source:Harvard University


Related biology news :

1. Quantum Dots Research Leads to New Knowledge about Protein Binding in Plants
2. Protein discovery could unlock the secret to better TB treatment
3. Researchers Uncover Key Step In Manufacture of Memory Protein
4. An HIV Protein Plays a Surprising Role in Gene Activation
5. New SARS Protein Linked To Important Cell Doorway
6. The Shapes Of Life: NIGMS Project Yields More Than 1,000 Protein Structures
7. PANTHER Protein Classification System Database 5.0
8. Duke Chemists Isolating Individual Molecules Of Toxic Protein In Alzheimers, Parkinsons Disease
9. Newly Discovered Compound Blocks Known Cancer-Causing Protein
10. UF Researchers Map Bacterial Proteins That Cause Tooth Loss
11. Protein offers way to stop microscopic parasites in their tracks
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/29/2016)... RATON, Florida , March 29, 2016 ... or the "Company") LegacyXChange "LEGX" and SelectaDNA/CSI Protect are ... DNA in ink used in a variety of writing ... theft. Buyers of originally created collectibles from athletes on ... through forensic analysis of the DNA. ...
(Date:3/22/2016)... India , March 22, 2016 /PRNewswire/ ... market research report "Electronic Sensors Market for Consumer ... Proximity, & Others), Application (Communication & IT, ... Geography - Global Forecast to 2022", published ... industry is expected to reach USD 26.76 ...
(Date:3/21/2016)... , March 22, 2016 ... recognition with passcodes for superior security   ... a leading provider of secure digital communications services, today ... biometric technology and offer enterprise customers, particularly those in ... facial recognition and voice authentication within a mobile app, ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... ... June 24, 2016 , ... Researchers at the Universita Politecnica ... in people with peritoneal or pleural mesothelioma. Their findings are the subject of a ... , Diagnostic biomarkers are signposts in the blood, lung fluid or tissue of ...
(Date:6/23/2016)... Mass. , June 23, 2016   ... development of novel compounds designed to target cancer ... napabucasin, has been granted Orphan Drug Designation from ... the treatment of gastric cancer, including gastroesophageal junction ... stemness inhibitor designed to inhibit cancer stemness pathways ...
(Date:6/23/2016)... , June 23, 2016 Houston Methodist ... the Cy-Fair Sports Association to serve as their ... agreement, Houston Methodist Willowbrook will provide sponsorship support, ... connectivity with association coaches, volunteers, athletes and families. ... the Cy-Fair Sports Association and to bring Houston ...
(Date:6/23/2016)... , June, 23, 2016  The Biodesign Challenge ... envision new ways to harness living systems and biotechnology, ... Art (MoMA) in New York City ... 130 participating students, showcased projects at MoMA,s Celeste Bartos ... Paola Antonelli , MoMA,s senior curator of architecture and ...
Breaking Biology Technology: