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 Seeing on the Quick: New Insights into Active Vision in the Brain
15.08.2018 | Eberhard Karls Universität Tübingen

nachricht New Approach to Treating Chronic Itch
15.08.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Unraveling the nature of 'whistlers' from space in the lab

15.08.2018 | Physics and Astronomy

Diving robots find Antarctic winter seas exhale surprising amounts of carbon dioxide

15.08.2018 | Earth Sciences

Early opaque universe linked to galaxy scarcity

15.08.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>