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 Antimicrobial substances identified in Komodo dragon blood
23.02.2017 | American Chemical Society

nachricht New Mechanisms of Gene Inactivation may prevent Aging and Cancer
23.02.2017 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

From rocks in Colorado, evidence of a 'chaotic solar system'

23.02.2017 | Physics and Astronomy

'Quartz' crystals at the Earth's core power its magnetic field

23.02.2017 | Earth Sciences

Antimicrobial substances identified in Komodo dragon blood

23.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>