What is it about?
We describe the DNA sequences that regulate genes that are expressed together in the same cell. We also show that these sequences are clustered in these coordinately regulated genes. These DNA sequence clusters also make buffer the gene against mutations that might prevent any one of the members of the cluster from performing its regulatory role.
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Why is it important?
There is an enormous amount of DNA sequence variation in the human genome. This variation both accounts for our normal genetic differences and can predispose in some people to different diseases. It is important to understand the effects of these variants, if any, for determining predisposition, diagnosis and treatment for disease. This study shows that individual variation in the DNA sequences that control gene expression is important for defining which genes are expressed coordinately. Single variants which would be expected to inactivate the expression of a gene or turn on genes that are ordinarily off in a particular tissue, in fact, don't have these effects. This is important because it suggests that small errors or mutations in our genomes are not sufficient to alter gene expression.
Perspectives
One way in which this study is novel is that we use a combination of information theory and machine learning to find these information dense clusters of DNA sequences. Information theory is the only method that accurately represents the actual DNA binding events that are needed to exert control over gene expression. This is because it is based on the strength of the binding between the proteins, transcription factors, that drive expression and the DNA itself. We use properties of these binding sites, that is their strength and distribution in these gene sequences to formulate a mathematical model which can find the genes targeted by the same transcription factor.
Dr Peter K Rogan
Western University
Read the Original
This page is a summary of: Transcription factor binding site clusters identify target genes with similar tissue-wide expression and buffer against mutations, F1000Research, December 2018, Faculty of 1000, Ltd.,
DOI: 10.12688/f1000research.17363.1.
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