Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein’s role in hemoglobin gene silencing identified

12.04.2006
Findings may point researchers to future targets for treatment of genetic blood disorders

Virginia Commonwealth University Massey Cancer Center researchers have identified the role of a protein in hemoglobin gene silencing that may one day be a potential target for the treatment of genetic blood disorders like sickle-cell anemia and beta-thalassemia on the molecular level.

In the April issue of the journal Proceedings of the National Academy of Sciences, researchers reported for the first time that the protein, MBD2, mediates silencing of the fetal gamma-globin gene through DNA methylation, a process that chemically modifies DNA. Researchers used a transgenic mouse model containing the human hemoglobin gene locus to show that MBD2 interprets the DNA methylation “signal” throughout the genome, which determined how the pattern of methylation effected the expression of specific genes.

“Understanding how these epigenetic switches turn specific genes on and off, and identifying the important proteins involved, could lead to more targeted ways to reactivate genes and determine if there is a therapeutic benefit for particular diseases,” said Gordon D. Ginder, M.D., director of the VCU Massey Cancer Center and lead author of the study.

Epigenetics refers to the study of the modifications of DNA and the surrounding proteins found in chromosomes that turn genes on and off and that can be passed on after cell division in an individual. Traditionally, researchers have focused their attention on changes to the DNA base code as being responsible for altered gene expression in disease.

Previous clinical studies have shown that increased gamma-globin gene expression has a positive effect in those with sickle-cell anemia or beta-thalassemia. “The gamma-globin genes normally become silent in adult hemoglobin expressing red blood cells. If we can find a specific and safe mechanism to reactivate the gamma-globin gene, we may be able to overcome the underlying molecular defect in sickle-cell anemia and beta-thalassemia,” Ginder said.

Gene silencing is important for the differentiation of many different types of cells to take place. In humans, there are five beta-type globin genes clustered on chromosome 11 in the order in which they are “turned on,” or expressed, during development. These genes include the embryonic epsilon-globin gene, two gamma-globin genes and the adult delta- and beta-globin genes. During fetal development, the embryonic epsilon-globin gene is active first, followed by the gamma-globin genes, and finally the major adult form, beta-globin, becomes the dominant expressed gene following birth.

According to Ginder, regulation of many genes and other molecular processes require DNA methylation. He said that DNA methylation is associated with the silencing of many types of genes, including tumor suppressor genes found in cancer cells. Scientists now know that DNA methylation plays a significant role in the development and progression of several forms of cancer.

Currently, the only therapeutic approach to relieving methylation-mediated gene silencing that has been tested in humans is through blocking the methylating enzymes non-specifically throughout the cell. Although this approach may have the desired effect on the specific gene or genes involved, it can also have an undesirable effect by turning on the wrong genes, he said.

“The more targeted the approach the better, because there is less likelihood of producing any unintended negative side-effects. For example, there is some specificity of how some proteins, such as MBD2, act to silence only certain sets of methylated genes,” Ginder said.

Mutations of hemoglobin genes play a role in genetic blood disorders such as sickle-cell anemia and beta-thalassemia.

This work was supported by a grant from the National Institutes of Health.

Ginder collaborated with VCU Massey Cancer Center researchers Jeremy W. Rupon, B.S., a combined M.D./Ph.D. student; Shou Zhen Wang, M.S., a research associate; and Joyce Lloyd, Ph.D., an associate professor of human genetics. Also Karin Gaensler, Ph.D., from the University of California collaborated on this work.

Sathya Achia-Abraham | EurekAlert!
Further information:
http://www.massey.vcu.edu
http://www.vcu.edu

More articles from Life Sciences:

nachricht Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>