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Tri-methylation of Histone H3 Lysine 4 Facilitates Gene Expression in Ageing Cells

Cristina Cruz, Monica Della Rosa, View ORCID ProfileChristel Krueger, Qian Gao, Lucy Field, View ORCID ProfileJonathan Houseley
doi: https://doi.org/10.1101/238048
Cristina Cruz
1Epigenetics Programme, The Babraham Institute, Babraham, Cambridge, UK
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Monica Della Rosa
1Epigenetics Programme, The Babraham Institute, Babraham, Cambridge, UK
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Christel Krueger
1Epigenetics Programme, The Babraham Institute, Babraham, Cambridge, UK
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Qian Gao
1Epigenetics Programme, The Babraham Institute, Babraham, Cambridge, UK
2Present address: Adaptimmune Ltd, 60 Jubilee Avenue, Milton Park, Abingdon, Oxfordshire, UK
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Lucy Field
1Epigenetics Programme, The Babraham Institute, Babraham, Cambridge, UK
3Present address: Molecular Haematology Unit, The MRC Weatherall Institute of Molecular Medicine, Oxford, UK
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Jonathan Houseley
1Epigenetics Programme, The Babraham Institute, Babraham, Cambridge, UK
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  • For correspondence: jon.houseley@babraham.ac.uk
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Abstract

Transcription of protein coding genes is accompanied by recruitment of COMPASS to promoter-proximal chromatin, which deposits di- and tri-methylation on histone H3 lysine 4 (H3K4) to form H3K4me2 and H3K4me3. Here we determine the importance of COMPASS in maintaining gene expression across lifespan in budding yeast. We find that COMPASS mutations dramatically reduce replicative lifespan and cause widespread gene expression defects. Known repressive functions of H3K4me2 are progressively lost with age, while hundreds of genes become dependent on H3K4me3 for full expression. Induction of these H3K4me3 dependent genes is also impacted in young cells lacking COMPASS components including the H3K4me3-specific factor Spp1. Remarkably, the genome-wide occurrence of H3K4me3 is progressively reduced with age despite widespread transcriptional induction, minimising the normal positive correlation between promoter H3K4me3 and gene expression. Our results provide clear evidence that H3K4me3 is required to attain normal expression levels of many genes across organismal lifespan.

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Posted December 22, 2017.
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Tri-methylation of Histone H3 Lysine 4 Facilitates Gene Expression in Ageing Cells
Cristina Cruz, Monica Della Rosa, Christel Krueger, Qian Gao, Lucy Field, Jonathan Houseley
bioRxiv 238048; doi: https://doi.org/10.1101/238048
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Tri-methylation of Histone H3 Lysine 4 Facilitates Gene Expression in Ageing Cells
Cristina Cruz, Monica Della Rosa, Christel Krueger, Qian Gao, Lucy Field, Jonathan Houseley
bioRxiv 238048; doi: https://doi.org/10.1101/238048

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