February 14, 2017 by Brian Wallheimer This stylistic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). The chromosome is X-shaped because it is dividing. Introns are regions often found in eukaryote genes that are removed in the splicing process (after the DNA is transcribed into RNA): Only the exons encode the protein. The diagram labels a region of only 55 or so bases as a gene. In reality, most genes are hundreds of times longer. Credit: Thomas Splettstoesser\/Wikipedia\/CC BY-SA 4.0 <\/p>\n
Purdue University and Indiana University School of Medicine scientists were able to force an epigenetic reaction that turns on and off a gene known to determine the fate of the neural stem cells, a finding that could lead to new therapeutics in the fight against select cancers and neural diseases. <\/p>\n
Joseph Irudayaraj, a Purdue professor of agricultural and biological engineering, and Feng Zhou, a professor and neuroscientist at the Indiana University School of Medicine, have developed an optogenetic toolbox that brings together proteins and enzymes that methylate or demethylate a gene called Ascl1. Alteration of the methylation pattern in a specific gene with the optogenetic proteins would allow scientists to turn that gene on or off and produce desirable neurons among other cell types. <\/p>\n
\"If we can alter the epigenetic state at a specific location of a gene, then we can turn that gene on or off for personalized medicine,\" Irudayaraj said. <\/p>\n
The findings, published in the journal Nature Scientific Reports, have implications for a number of diseases and maladies. <\/p>\n
\"By the ability of determining the fate of stem cells, one day it may be applied to produce neurons in Down syndrome, or reduce malignancy of glioma, a cancer in the brain,\" Zhou said. \"By altering the methylation marks at a specific location of the gene, we have shown that the state of a cell can be altered.\" <\/p>\n
Epigenetics is the study of changes in chemical modifications on top of a gene based on external or environmental factors rather than changes in a DNA sequence. Optogenetics involves the utilization of light-sensitive proteins to alter the genetic or epigenetic profile in a cell or organism. <\/p>\n
The researchers' findings detail the ability to modify the methylation profile of the Ascl1 gene in a site-specific manner, thereby controlling gene expression. DNA methylation involves adding a methyl group to the cytosine base of DNA, utilizing a family of enzymes called DNA methyltransferases (DNMTs). DNA demethylation is the removal of a methyl group from the cytosine bases using enzymes called Ten-Eleven Translocation, or TET. <\/p>\n
Irudayaraj and his team attached these cytosine-modifying enzymes DNMT3A\/TET to light-sensitive protein pairs to demonstrate site-specific methylation\/demethylation. Zhou and his team introduced those light-sensitive proteins into neural stem cells and found that when they shined a blue light, the methylation modifying enzyme DNMT3A\/TET and the gene target came together, adjusting the methylation of the gene. <\/p>\n
\"It's almost like putting a worm on a hook, and putting it in the water to catch a fish when it comes along. Once the light goes on, the hook and the fish come together and you catch the fish,\" Irudayaraj said. <\/p>\n
The ability to activate or deactivate a gene, specifically those that suppress or promote a disease condition, could be a valuable tool for cancer therapeutics as well. The team plans to take the findings, done on neural stem cells, to mouse model systems. <\/p>\n
\"We want to apply this to therapeutics or toxicology,\" Irudayaraj said. \"Essentially the applications are very broad. It can also include nervous system malfunctions, including addiction.\" <\/p>\n
Explore further: Epigenetics and neural cell death <\/p>\n
More information: Chiao-Ling Lo et al. Epigenetic Editing of Ascl1 Gene in Neural Stem Cells by Optogenetics, Scientific Reports (2017). DOI: 10.1038\/srep42047<\/p>\n
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See the article here: February 14, 2017 by Brian Wallheimer This stylistic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). Continue reading
\nOptogenetics used to kick start gene that plays role in neural defects - Medical Xpress<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"