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A study published in the journal Molecular Biology and Evolution shows that the global gene regulator GABPa is controlling uniquely human genes – and may contribute to diseases like Parkinson’s.
The team, led by Robert Querfurth, explored the gene regulator – known as a transcription factor in scientific language – to understand its role as a master switch in human gene regulation. They started by investigating which genes are under the influence of the transcription factor, observing that binding sites for the regulator were common in genes that are important for central nervous system functions unique to humans.
GABPa exerts its action by binding to a so-called tandem repeat; a sequence of four DNA bases that is conserved among all primates as well as in cats, dogs and cows. The team used ChIP-Seq – a technique for identifying genome-wide binding sites in the DNA-binding transcription factors. They found that GABPa had 11,619 binding sites spread across 4,000 genes in the different species.
By comparing the DNA of 34 mammals to humans, they found 224 GABPa binding sites unique to humans. They further explored the function of the regulator by comparing the effects of the transcription factor – as well as mutated forms resembling ancestral states of the regulator – in chimpanzee, macaque, and human cultured cells.
The team introduced a human version of a GABPa binding site into primate cells and saw that the transcription of the genes under control of the regulator was increased. This suggests that a mutation in the GABPa drove the evolution of uniquely human characteristics – and possibly also diseases. “Mutations that cause changes in the regulation of gene activities are one of the major factors in shaping species during evolution,” Querfurth said in a press release. “Our study demonstrates how, out of the millions of DNA regions in which we differ from other apes, we can sift out those that, in response to a specific regulatory protein, cause gene activity changes in human cells. In this set, we find genes involved in brain and breast development and also in diseases like Alzheimer’s and Parkinson’s.
http://parkinsonsnewstoday.com/2016/01/29/gabpa-a-driving-force-behind-human-evolution/
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