Scientists flag up new gene switches

The complex development and behaviour of mammals lies not in the number of their genes, but in how those genes are controlled. Mammalian genomes are full of switches that determine when, where and how genes are switched on, but we do not know how many switches there are and where they are located in our genome.

One way that scientists have sought to find our genetic switches is by focusing on chromatin – the protein wrapper that acts as a form of packaging for DNA and carries epigenetic information.

It was previously understood that when a genetic switch is activated, this packaging develops a chemical flag that acts as a signal to recruit other proteins. It was thought that by mapping where this one type of flag signal is located in our genome, we could catalogue the active genetic switches in a cell.

This study, led by the MRC Human Genetics Unit at the University of Edinburgh, shows that in fact there is a previously undiscovered set of switches that carry a different type of flag, which can physically disrupt the structure of the packaging around DNA.

The findings help scientists to understand how genes are controlled. They are also important for understanding how the human genome impacts on health and disease.

Most of the genetic variation in the human population that affects the risk of developing common diseases – such as cancer, stroke, diabetes and arthritis – is not in genes themselves, but in the ‘control’ elements that switch genes on.

Lead researcher Professor Wendy Bickmore said: “The big challenge for human geneticists today – especially as we sequence the entire genome of tens of thousands of people – is to understand where the controlling elements important for health and disease are located amongst the vast tracts of our non-coding genome. Our new finding helps to flag up where to look.”

The study has been published in Nature Genetices.

The work was conducted in partnership with the Institute of Functional Epigenetics in Munich. It was funded by the Medical Research Council.

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