Genetic Variations Determine Actions of Gene Regulatory Factors, Mouse Study Reveals

Genetic Variations Determine Actions of Gene Regulatory Factors: A recent study from the University of Eastern Finland found that our genes play a role in determining how easily certain parts of our DNA can be accessed, which in turn affects how genes are expressed. This study focused on chromatin, a combination of DNA and proteins, and how tightly it is packaged. Transcription factors, proteins that regulate gene activity, are responsible for controlling this packaging.

The research discovered that most genetic variations linked to the risk of complex diseases occur in areas outside the protein-coding parts of genes. Transcription factors need to bind to specific DNA sequences within chromatin, and changes to these sequences can impact gene expression. Scientists often use chromatin accessibility to identify locations where these regulatory factors bind.

To study this, researchers compared the behavior of gene-regulating regions and gene expression in the liver, as well as responses to a high-fat diet, in two different types of mice. These mice are commonly used in studying obesity and type 2 diabetes.

Interestingly, no differences were found in chromatin accessibility between the two types of mice when on a regular or high-fat diet. However, significant differences were observed between the mice, particularly in chromosomal locations where genetic differences were present. These differences often occurred near genes that were expressed differently between the two types of mice, indicating that genetic variation influenced the binding of transcription factors and, consequently, gene expression.

The study also looked into predicting changes caused by genetic variation in the binding sites of transcription factors. The best predictions came from combining data on chromatin accessibility, genetic variation, and binding regions of transcription factors. However, when the same genetic variation affected the binding sequences of multiple transcription factors, the predictions were less reliable. Therefore, it’s crucial to directly measure the impact of genetic variation on each transcription factor’s binding.

In summary, this research enhances our understanding of how genetics, modifications to chromatin, and the actions of transcription factors are interconnected in controlling gene expression. The study also highlights the potential use of public datasets to investigate the mechanisms behind the hereditary risk factors for complex diseases, according to University Teacher Juho Mononen from the University of Eastern Finland.

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