Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

When DNA Gets Sent to Time-Out

08.01.2015

New details revealed in the coordinated regulation of large stretches of DNA

Fast Facts:
• Directly inside the membrane of the cell’s nucleus is a meshwork of proteins called the lamina.
• Genes are turned off in large stretches of DNA that attach to the lamina.
• New work reveals what is needed to get DNA to stick, shedding light on how the body regulates its genes.


Reddy Lab, Johns Hopkins Medicine

In mouse cells, the YY1 protein binds to a segment of DNA (green), leading it to attach to the lamina (red) at the edge of the nucleus.

For a skin cell to do its job, it must turn on a completely different set of genes than a liver cell — and keep genes it doesn’t need switched off. One way of turning off large groups of genes at once is to send them to “time-out” at the edge of the nucleus, where they are kept quiet. New research from Johns Hopkins sheds light on how DNA gets sent to the nucleus’ far edge, a process critical to controlling genes and determining cell fate.

A report on the work appeared in the Jan. 5 issue of the Journal of Cell Biology.

“We discovered a DNA sequence and a specific set of protein tags that send DNA to the edge of the nucleus, where its genes get turned off,” says Karen Reddy, Ph.D., an assistant professor of biological chemistry at the Johns Hopkins University School of Medicine.

Picture the nucleus as a round room filled with double strands of DNA hanging in suspension as they are opened, closed, clipped, patched and read by proteins that come and go. At the edge of the nucleus, just inside its flexible walls, the lamina meshwork provides shape and support. But accumulating evidence from the past few years suggests that this meshwork is not just a structure, but is crucial to the cell’s ability to turn large segments of genes off in one fell swoop. It’s as though certain stretches of DNA feel a magnetic pull that keeps them clinging to the lamina in a state of “time-out,” inaccessible to the proteins that could be working on them.

This method of turning off entire segments of the genome is particularly useful during development, when each cell in the embryo takes on a different fate by making a different set of proteins, even though each contains the same set of genes. What was unknown is what marks a particular DNA segment to be sent to the lamina for some “quiet time.”

Reddy and her team began answering that question by comparing immature, embryonic, skinlike cells to mature immune system cells from mice. When they compared the segments of DNA clinging to the lamina in the two cell types, they found that differences occurred near genes that are used differently between the two. Additionally, the DNA regions that cling to the lamina were very consistent; there were no “grey areas” that were only sometimes associated with the lamina.

Next, the researchers chopped up the lamina-associated DNA segments and inserted individual pieces into the chromosomes of test cells, watching for the nearby chromosome segments to move to the lamina. They found that these segments were able to bind the protein YY1, and that YY1, when bound to a segment of DNA, was able to send the surrounding DNA to the lamina.

Reddy’s team also discovered two molecular tags that are needed for DNA to move to the lamina. The tags are found on the histone proteins that DNA coils around and are a classic form of “epigenetic regulation” — gene regulation that does not involve DNA sequence changes. It seems likely that YY1 is involved in summoning the proteins that attach the molecular tags to the histones. But whether YY1 has additional roles, like acting as a magnet to bring the DNA to the lamina, is unclear.

“This is the first time a specific combination of epigenetic modifications has been implicated in tethering DNA to the lamina,” says Reddy. “Now we have a lot of interesting questions to answer about how different types of cells use this mechanism to regulate different sets of genes.”

Other authors of the report include Jennifer Harr, Teresa Romeo Luperchio, Xianrong Wong, Erez Cohen and Sarah Wheelan of the Johns Hopkins University School of Medicine.

This work was supported by a grant from the National Institute of General Medical Sciences (1 R01 GM106024-01).

Contact Information
Catherine Kolf
Senior Communications Specialist
ckolf@jhmi.edu
Phone: 443-287-2251
Mobile: 443-440-1929

Catherine Kolf | newswise
Further information:
http://www.jhmi.edu

Further reports about: DNA DNA sequence Johns Hopkins YY1 fate genes molecular tags proteins

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 >>>