Study shows how hormones and cancer drugs shape human genome

Image

Our genes are controlled by hundreds of thousands of genetic switches – known as enhancers – which are often located in the genome far from the genes they control.

How enhancers talk to their target genes across long distances is not clear, but it is thought to involve three-dimensional folding of the genome, bringing enhancers and genes close together.

Researchers at the MRC Human Genetics Unit used imaging and molecular ‘chromosome conformation capture’ techniques to examine how 3D human genome organisation is reshaped by the female hormone oestrogen in breast cancer cells.

The activation of enhancers by oestrogen resulted in the detection of protein bridging between enhancers and genes but, unexpectedly, also pushed enhancers and genes further away from each other in the cell nucleus.

This did not occur when the cells were exposed to tamoxifen, a modulator of oestrogen signalling used in the treatment of some breast cancers. The surprising spatial separation of enhancers and genes was also shown to depend on the production of RNA.

This work suggests that there is a need for further investigation into how other drugs used in the treatment of oestrogen-responsive cancers affects the 3D re-organisation of the human genome.

Luciana Gómez Acuña

Links

• Full article DOI: https://doi.org/10.1371/journal.pgen.1011277
• Bickmore lab