What Turns Genes On and Off?

     A team of researchers from Perelman School
of Medicine at University of Pennsylvania have
shed light on how structure of regulatory sequences in DNA is packaged in a cell. The research gives a better understanding of how gene sequences, contribute to gene activity. Enhancers are what influences genes in each cell to be turned on or off. The ultimate purpose of this is to dictate the quality of an encoded protein that is made in response to a physiological change. The following link gives further insight to gene expression and how they can be turned on and off. One reason this research is so important is that many studies have shown errors in enhancers lead to disease or cancer.

      Nucleosomes are a protein that DNA winds around in every cell, and in the past it was believed that when nucleosomes are present the surrounding genes are turned off; therefore not playing a role at enhancer sites. This study provides data to dispute this recently believed theory, and nucleosomes are present at enhancer sites.

     The team of researchers found that certain stretches of DNA were bound to nucleosomes and could be modified to have genes turned on. They removed linker histones from DNA, and allowed enhancers to activate that a single gene which caused the cell to function normally. The team believes this is very promising, because with these techniques cancers and disease can be fought. Also it can be useful in embryo therapy.

      I agree that this study shows very promising results. If scientist can learn to completely turn genes on or off it will cause medical break throughs. It will gives doctors a new angle on fighting disease and forms of cancer. These advancements can also help correct errors in developing embryos or fetuses.

DNA Packaged Like Yoyo

Scientists recently reported in Cell that DNA's sequence causes it to be coiled and uncoiled much like a yoyo. "We discovered this interesting physics of DNA that its sequence determines the flexibility and thus the stability of the DNA package inside the cell," said Gutgsell Professor of Physics Taekjip Ha, who is a member of the Carl R. Woese Institute for Genomic Biology at the University of Illinois. He goes on to say how many people thought this should have been known decades ago but that there are still surprises in the physics of DNA being discovered. 

We know that a string of DNA is coiled around histones to create nucleosomes. Then these nucleosomes are braided together into strings that are woven into chromosomes. Scientists assumed that when DNA was uncoiled from these nucleosomes that the two ends were symmetric, meaning that the DNA would uncoil like the untying of a shoe. However, University of Illinois researchers found that DNA is actually asymmetric, making it like the string wrapped around a yoyo. Pulling one end of the DNA would tighten the coil while pulling the other would cause it to uncoil like a yoyo.

The physics of this nucleosome packaging is determined by the DNA's sequence which makes the strand of DNA flexible enough to be stable to compact DNA and dynamic so the strand can be uncoiled and read to make proteins. The research showed that it is easier for the cell's protein making machinery to read from the "weak" end of the nucleosome that uncoils more easily. It is now thought that genetic mutations related to diseases, like cancer, alter the stability of the nucleosome. Professor Ha now plans to use next generation sequencing to determine the flexibility of an entire genome and hopes to create the first genome-wide map of physical properties.

I thought this information was very interesting to learn since it seems like something that we should have known for a much longer time with the technology we have available today. Also, this shows how their is always evolving information just waiting to be discovered. Furthermore, I think that by developing a way to make certain strands of harmful DNA the "stronger" end, so that the "weaker" end is coded, we could possibly stop certain diseases. 

Original Article- http://www.sciencedaily.com/releases/2015/03/150316160712.htm

Link Between DNA Transcription, Disease-Causing Expansions

     Scientists have known that long nucleotide base repeats in the human genome have led to heritable human diseases such as Huntington’s disease. Huntington’s disease is a neurodegenerative disease that affects muscle coordination and leads to a deterioration of cognitive thought. There are many nucleotide base repeats that are stable, but their lengthening over time leads to genome instability and changes in gene expression which can cause these diseases. Up until now, it was thought that the lengthening of these nucleotide base repeats was caused during DNA replication or when DNA repair machinery was active in the cell. However, it was found that the lengthening of these base pair repeats also occurs during transcription, which is the process of forming RNA from a DNA template within a cell.

                    

In a study performed by a research team led by Sergei Mirkin, the White Family Professor of Biology at Tufts' School of Arts and Sciences, the correlation between transcription and the expansion of base pair repeats was observed in yeast. The team used genetic systems to track the lengthening of nucleotide base pair repeats during DNA replication, DNA repair, and transcription. These genetic systems were also used to track the number of expansions in transcribed and non-transcribed parts of reporter genes. It was found that both transcribed and non-transcribed fragments of the reporter genes showed expansion, but the transcribed form of the reporter genes was ten times more likely to undergo the expansion process. This is because in a transcriptionally active state, the transcribed DNA segment has significantly less nucleosome density which leaves more room for repeat expansions of nucleotide base pairs.

                                      
     I find this article interesting because it relates the expansion of nucleotide base pairs to heritable diseases such as Huntington’s. By learning more about what causes these diseases, more efficient methods of treatment or cures can be discovered and implemented.

Source: Link Between DNA Transcription, Disease-Causing Expansions