Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Location matters, even for genes

14.02.2008
Moving an active gene from the interior of the nucleus to its periphery can inactivate that gene report scientists from the University of Chicago Medical Center in an article to be published early online Feb.13, 2008, in the journal Nature.

Attachment to the inner nuclear membrane, they show, can silence genes, preventing their transcription--a novel form of gene regulation.

"Several years ago, we and others described the correlation between nuclear positioning and gene activation," said study author Harinder Singh, Louis Block Professor of Molecular Genetics and Cell Biology and an Investigator in the Howard Hughes Medical Institute at the University of Chicago.

"With that in mind, we wanted to take the next step, to design an experiment that could test causality. Could we move a gene from the center of the nucleus to the periphery, we asked, and then measure the consequences of such repositioning?"

... more about:
»Interior »Membrane »Nucleus »Singh »inner »periphery

In mammalian nuclei, chromatin--a complex of DNA and associated proteins--is organized into structural domains through interactions with distinct nuclear compartments. In this study, the authors developed the molecular tools to take specific genes from these interior compartments, move them to the periphery and attach them to the nuclear membrane--which turned those genes off.

Not only were selected "test" genes that served as markers turned off after being attached to the inner nuclear membrane, but also nearby "real" genes.

Singh’s laboratory had become interested in studying the role of nuclear postioning in the control of gene activity based on work analyzing immunoglobulin heavy-chain genes. These genes are assembled by DNA recombination and code for proteins that are a crucial part of antibodies, produced in antibody-secreting lymphocytes or B-cells.

"In cells that don’t produce antibodies, like fibroblasts or T-cells, these antibody genes are attached to the inner nuclear membrane and are not recombined or expressed," said Singh.

On the other hand, antibody genes are actively transcribed and recombined in developing B-cells, and therefore positioned in the nuclear interior, far away from the periphery.

Five years ago, Singh and colleagues reported in Science that even in developing B cells, antibody genes start off at the nuclear periphery. As young cells mature and prepare to produce antibodies, however, these genes move to the interior of the nuclei.

The exact ways in which positioning at the outer edge of the nucleus prevents gene expression are still unclear. The likely suspects, said Singh, are some of proteins that reside in the inner nuclear membrane.

These proteins may be involved in blocking transcription, he said. They accumulate at sites of attachment and come in contact with parts of certain silenced genes. "So we think that these proteins are part of the molecular machinery that is used for positioning genes at the inner nuclear membrane, as well as potentially for repressing them,” he said.

In their Nature paper, Singh's team also showed for the first time that this transcriptional repression was dependent on breakdown and reformation of the nuclear membrane during cell division.

The reorganizing of chromosomes occurs when cells divide. "This suggests that cell division is used not only to transmit the genetic information into daughter cells and create two equivalent cells," he said, "but it is also an opportunity for cells to reorganize their genomes in 3D space, sequestering parts of the genome at the nuclear periphery and rendering it inaccessible to transcription.”

Singh and colleagues are now looking for examples of striking reorganization of the genome separated by one cell division--in which active genes, that will not be active after the cell divides, get pushed away from the interior to the periphery.

The lead author, Karen Reddy, a postdoctoral fellow in the Singh laboratory, proposes that, such compartmentalization "implies the existence of DNA segments that encode for ‘nuclear addresses’ acting like a nuclear zip code to direct or predispose genes to associate with specific regions within the nucleus. This could be tremendously important," she said, "for understanding the underlying cause of some diseases that result from mutations in genes encoding inner nuclear membrane proteins."

John Easton | EurekAlert!
Further information:
http://www.uchospitals.edu

Further reports about: Interior Membrane Nucleus Singh inner periphery

More articles from Life Sciences:

nachricht Microscope measures muscle weakness
16.11.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

nachricht Good preparation is half the digestion
16.11.2018 | Max-Planck-Institut für Stoffwechselforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

Purdue cancer identity technology makes it easier to find a tumor's 'address'

16.11.2018 | Health and Medicine

Good preparation is half the digestion

16.11.2018 | Life Sciences

Microscope measures muscle weakness

16.11.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>