Navigation Links
Uncovering the genome's regulatory code
Date:9/10/2012

Since the sequencing of the human genome in 2001, all our genes around 20,000 in total have been identified. But much is still unknown for instance where and when each is active. Next to each gene sits a short DNA segment, and the activity of this regulatory segment determines whether the gene will be turned on, where and how strongly. These short regulatory segments are as if not more important than the genes, themselves. Indeed, 90% of the mutations that cause disease occur in these regulatory areas. They are responsible for the proper development of tissues and organs, determining, for instance, that eye cells and only eye cells contain light receptors, while only pancreatic cells function to produce insulin. Clearly, a deeper understanding of this regulatory system its mechanisms and possibilities for malfunction may lead to advances in biomedical research, especially in developing targeted therapies for individual patients.

In spite of their importance, the "regulatory code" is not well understood. To address this problem, a research team led by Dr. Ido Amit of the Weizmann Institute Immunology Department, together with scientists from the Broad Institute in Massachusetts, including Manuel Garber, Nir Yosef and Aviv Regev, and Nir Friedman of the Hebrew University of Jerusalem, developed an advanced, automated system for mapping these sites, and then used this system to uncover important principles how these regulatory elements function. Among other things, their study, which appeared in Molecular Cell, revealed a hierarchical structure for the regulatory code. By mapping a large number of regulatory factors, the team succeeded in revealing an overall plan for gene regulation as well as the intimate details of the mechanisms involved in the immune response.

"We are seeing a race to map the regulatory code and uncover its ties to disease and human variation that is reminiscent of the race to sequence the human genome," says Amit. "But until now, participants have faced a serious hurdle: The process used for the past 30 years to map regulatory elements has been complicated, complex and labor-intensive, requiring huge scientific consortiums. With the new method, just a handful of researchers were able to conduct a study on a similar scale to the mega-team ones, and in a fraction of the time."

Their highly efficient, automated method enabled Amit and his team to measure a large number of regulatory proteins and their binding sites in parallel. They exposed immune cells to bacteria setting the stage for gene activation and then traced the actions of several dozen different regulatory proteins known to play a role in the immune response over four points in time. Not only were the researchers able to identify the binding locations of each and the genes they activate, but the levels of activation and the mechanisms employed.

One of their more significant findings was that the actions of these regulatory factors can be neatly classified into three levels in a sort of regulatory hierarchy. In the bottom tier are those factors that create the rough divisions into main cell types by directing cell differentiation. These factors are the "basic identity" guides that can, on their own, determine whether a cell will have the characteristics of a muscle cell, a nerve cell, etc. On the second tier are the regulatory factors that determine a cell's sub-identity, which they do by controlling the strength of a gene's expression. These factors are in charge of producing closely-related sub-types, for instance, muscle fibers that are either smooth or striated, or closely-related immune cells. Regulatory factors in the third tier are even more specialized: They only affect the expression of certain genes that are called into action in response to signals from outside the cell: bacterial invaders, hormones, hunger pangs, etc.

The hope is that understanding the ins and outs of the regulatory code will help researchers to understand and predict how diseases arise and progress due to malfunctions in regulatory mechanisms. In the future, understanding the regulatory program may lead to advances in rehabilitative medicine. Regulatory mechanisms could be used to redirect the differentiation of a patient's cells, which could then be reimplanted, thus avoiding the problems inherent in using donor cells.

Amit: "The new method for mapping the gene's regulatory plan may open new vistas for investigating all sorts of biological processes, including the system failures that occur in disease."


'/>"/>
Contact: Yivsam Azgad
news@weizmann.ac.il
972-893-43856
Weizmann Institute of Science
Source:Eurekalert

Related biology news :

1. Thirty teams compete to interpret three families genomes
2. Differences in the genomes of related plant pathogens
3. Researchers announce GenomeSpace environment to connect genomic tools
4. Athletic frogs have faster-changing genomes
5. New research reveals challenges in genetically engineered crop regulatory process
6. Study demonstrates cells can acquire new functions through transcriptional regulatory network
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/20/2016)... -- Securus Technologies, a leading provider of civil ... investigation, corrections and monitoring announced that after exhaustive ... the final acceptance by all three (3) Department ... (MAS) installed. Furthermore, Securus will have contracts for ... October, 2016. MAS distinguishes between legitimate wireless device ...
(Date:6/9/2016)... Paris Police Prefecture ... solution to ensure the safety of people and operations in ... major tournament Teleste, an international technology group specialised ... today that its video security solution will be utilised by ... public safety across the country. The system roll-out is scheduled ...
(Date:6/2/2016)... NEW YORK , June 2, 2016   The ... (Weather), is announcing Watson Ads, an industry-first capability in which ... advertising, by being able to ask questions via voice or ... Marketers have long ... with the consumer, that can be personal, relevant and valuable; ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... -- Global demand for enzymes is forecast to grow ... billion.  This market includes enzymes used in industrial ... animal feed, and other markets) and specialty applications ... beverages will remain the largest market for enzymes, ... containing enzymes in developing regions.  These and other ...
(Date:6/27/2016)... ... 2016 , ... Parallel 6 , the leading software as a service ... Virtual Patient Encounter CONSULT module which enables both audio and video telemedicine communication ... , Using the CONSULT module, patients and physicians can schedule a face to face ...
(Date:6/27/2016)...   Ginkgo Bioworks , a leading organism ... today awarded as one of the World Economic ... most innovative companies. Ginkgo Bioworks is engineering biology ... world in the nutrition, health and consumer goods ... customers including Fortune 500 companies to design microbes ...
(Date:6/24/2016)... ... 24, 2016 , ... Researchers at the Universita Politecnica delle Marche in Ancona ... or pleural mesothelioma. Their findings are the subject of a new article on the ... are signposts in the blood, lung fluid or tissue of mesothelioma patients that can ...
Breaking Biology Technology: