Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Pushmi-pullyu of B-Cell Development Discovered

26.06.2009
Although every cell in the body carries the genes necessary to function as an antibody-producing B cell, only a small proportion of stem cells mature into those important immune-system cells.

James Hagman, PhD, Professor of Immunology at National Jewish Health and his colleagues have identified two "molecular motors" that work in opposing directions to control the development of B cells. They published their findings June 19 in the online version of The Proceedings of the National Academy of Sciences USA.

"We found that these two ‘chromatin remodeling complexes' work in a sort of pushmi-pullyu manner to induce or retard epigenetic changes that allow for the development of a B cell," said Hagman. The pushmi-pullyu was a fictional animal in the Dr. Doolittle stories that had a head at opposite ends of its body, each pulling in a different direction. "The complexes help control both the unspooling of DNA to make genes accessible and the demethylation of DNA that removes silencing markers."

Although DNA in every cell contains the genes necessary to become B cells, two factors help keep them silent. One is the fact that the two meters of DNA inside a tiny cell nucleus is wrapped around millions of tiny spools, linked together like a string of pearls, which help keep the hereditary molecule from becoming irretrievably tangled. When wrapped tightly around these spools, individual genes are inaccessible to the molecules that bind and activate them. Second, many of the genes have small methyl groups, a carbon and three hydrogen atoms (CH3), on their DNA in specific places, which also prevent them from being activated. These factors are considered epigenetic states, modifications to existing DNA that control their activation or silencing.

Dr. Hagman and his colleagues previously identified a protein, known as Early B-cell Factor or EBF, which they dubbed a ‘pioneer factor.' By altering the epigenetic state of several genes, it is estimated that EBF can turn on hundreds of genes necessary for B-cell development. The researchers did not know, however, how EBF controlled those epigenetic factors.

They suspected that two chromatin remodeling complexes, conglomerations of several different proteins known to burn energy and physically move the tiny spools holding DNA, played a role. In a series of cell-culture experiments they showed that the two chromatin remodeling complexes, SWI-SNF and Mi2/NuRD, had opposing effects.

Transcription of a B-cell gene increased 70-fold when a cell contained both EBF and the two chromatin remodeling complexes. When the researchers inactivated the SWI/SNF complex, that activation fell to 8-fold, suggesting that SWI/SNF helped promote B-cell development. When they inactivated Mi-2/NuRD instead, expression of the B-cell gene increased 1,727-fold. Mi-2/NuRD was apparently acting as a brake, and its removal vastly increased expression of the B-cell gene.

Additional experiments showed that these two CRCs influenced the arrangement of DNA on the tiny histone spools inside the cell nucleus and the methylation of the B-cell gene.

"We knew that the two complexes were capable of influencing the arrangement of histone spools and accessibility of different genes, but were pleasantly surprised that they also affected the methylation state of the genes," said Dr. Hagman.

William Allstetter | EurekAlert!
Further information:
http://www.njc.org

More articles from Life Sciences:

nachricht Complementing conventional antibiotics
24.05.2018 | Goethe-Universität Frankfurt am Main

nachricht Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
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

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

First chip-scale broadband optical system that can sense molecules in the mid-IR

24.05.2018 | Physics and Astronomy

Beyond the limits of conventional electronics: stable organic molecular nanowires

24.05.2018 | Power and Electrical Engineering

These could revolutionize the world

24.05.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>