Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Protein’s role in hemoglobin gene silencing identified

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:

More articles from Life Sciences:

nachricht ‘Farming’ bacteria to boost growth in the oceans
24.10.2016 | Max-Planck-Institut für marine Mikrobiologie

nachricht Calcium Induces Chronic Lung Infections
24.10.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Oasis of life in the ice-covered central Arctic

24.10.2016 | Earth Sciences

‘Farming’ bacteria to boost growth in the oceans

24.10.2016 | Life Sciences

Light-driven atomic rotations excite magnetic waves

24.10.2016 | Physics and Astronomy

More VideoLinks >>>