Wednesday, 7 January 2015

Putting DNA In The ‘Sin Bin’

[caption id="attachment_169" align="alignright" width="300"]It's a pretty neat green dot beside a red line. A DNA segment (green) is led by YY1 to the lamina at the edge of the nucleus (red). Image credit: Reddy lab, Johns Hopkins Medicine.[/caption]

Key players that inactivate DNA by sending it to a sin bin in the nucleus have been identified in new research from Johns Hopkins University of Medicine, published this week. The team discovered that epigenetic factors were responsible for this mechanism of DNA silencing which helps determine cell types during development.

Each of our cells contains a full copy of our DNA, which codes for all of our genes. However, a brain cell is a far cry from a skin cell and naturally different cell types don’t use all of the same genes. The ability to turn on and, more importantly, off appropriate genes is essential for immature cells to grow into the specialised tissue cells found in organs like the brain, liver and kidneys.

One way of switching off genes en masse is for the cells to simply make the DNA inaccessible to the proteins that read genes. DNA is pushed to the edge of the nucleus, the envelope that contains the DNA, where it is silenced by interacting with a mesh-like structure called the lamina.

Dr Karen Reddy, lead author on the study, says “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.”

They found a protein, YY1, was responsible for interacting with DNA in sending it to the lamina. The team also discovered molecular tags on histones, proteins that DNA coil around in the nucleus, which were necessary for bringing DNA to the lamina. They believe that YY1 is indirectly involved in the tagging process, which would earmark sections of DNA for movement to the lamina.

Another point the authors found interesting was that this process of gene silencing was down to the sole activity of proteins, rather than changes to the DNA sequence. This kind of regulation is referred to as epigenetic regulation. “This is the first time a specific combination of epigenetic modifications has been implicated in tethering DNA to the lamina,” adds Dr Reddy. The team is now focusing on how different cells use this system to regulate different sets of genes.

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