Ageing well depends on tight gene control

Key points:

• Research confirms essential role of a common epigenetic mark in maintaining correct gene expression throughout the lifespan of budding yeast.
• H3K4me3 is present at the promoter of all expressed genes in all studied eukaryotes, but the importance of this mark in controlling gene expression has remained largely unknown.
• H3K4me3 is critical for the full expression of many genes that are induced in yeast with age and is important for normal lifespan.

Not all genes in the genome can or should be used in a particular cell type or environment. The genome operates in a ‘pick and mix’ fashion; selective and balanced expression of genes allows cells to perform a specific function or respond to a particular environmental challenge. Genes are tagged as ‘in use’ or ‘not in use’ by the use of epigenetic marks added to the genome. One particular epigenetic mark has been shown by Institute researchers to be important for normal lifespan in yeast. The findings of their research are published in the journal eLife today.
 

Research carried out in Jon Houseley’s lab studied yeast cells to confirm the role of a master epigenetic modification responsible for maintaining gene expression throughout their lifespan. H3K4me3 is present near the start sites of every gene expressed in organisms from algae to all animals. H3K4me3 is shorthand for indicating the addition of three small chemical methyl groups (me3) to the lysine 4 amino acid (K4) of a histone H3 protein. The researchers observed a dramatic reduction in lifespan in yeast cells lacking the epigenetic mark, with only 50% of these cells being viable at 24 hours old compared to 100% of wild type cells. At the molecular level, these yeast showed reduced expression of many genes which are activated during yeast ageing. Rather than this loss slowing ageing, this result shows that expression of these genes is important to protect against the ageing process.
 

“The importance of epigenetic marks in tightly regulating the activity of each gene in the genome is underlined by the dramatic reduction in lifespan of cells lacking this particular epigenetic mark” said Epigenetics Group Leader Dr Jon Houseley. “Understanding epigenetic marks is important for understanding how cells respond and adapt to different environments. This is a step towards understanding medically relevant cell adaptation events, such as the process by which some cancer cells withstand drug treatment.”
 

The new findings show that H3K4me3 is important to drive the expression of many genes that are not expressed under normal conditions but which are important for cell fitness in changing circumstances. Understanding the mechanism of how this happens will be part of future studies by Dr Houseley and his team into age-linked gene expression changes.
 

Notes to Editors

Publication reference
Cruz, C., and Della Rosa, M., et al. Tri-methylation of Histone H3 Lysine 4 facilitates gene expression in ageing cells. eLife
https://doi.org/10.7554/eLife.34081
 
 

Research funding
This research was supported by funding from the Wellcome Trust, the BBSRC, and the ERC (EpiGeneSys Network). Use of the Institute’s Sequencing and Bioinformatics facilities was supported by the Institute’s Core Capability Grant from the BBSRC.
 
 

Press contact
Dr Louisa Wood, Institute Communications Manager, louisa.wood@babraham.ac.uk
 
 

Related news:
Microbes may rig their DNA to speed up evolution. Article in Wired magazine, August 2017
Directed gene-copy variation: the key to conquering new environments. Institute news June 2017
 
 

Image description:
Hand holds a petri dish containing yeast (Shutterstock/Trinset 602107850)

Affiliated authors (in author order):
Cristina Cruz, Houseley group, Epigenetics research programme
Monica Della Rosa
Christel Krueger, Babraham Bioinformatics Facility
Qian Gao, previous member of the Houseley group
Dorottya Horkai, Houseley group, Epigenetics research programme
Michelle King, Houseley group, Epigenetics research programme
Lucy Field, previous member of the Houseley group
Jonathan Houseley, Group Leader, Epigenetics research programme
 
 

About the Babraham Institute
The Babraham Institute undertakes world-class life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Our research focuses on cellular signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing. The Institute is strategically funded by the Biotechnology and Biological Sciences Research Council (BBSRC) through an Institute Core Capability Grant and also receives funding from other UK research councils, charitable foundations, the EU and medical charities.