Publications by authors named "Dorottya Horkai"

2 Publications

  • Page 1 of 1

Tri-methylation of histone H3 lysine 4 facilitates gene expression in ageing cells.

Elife 2018 10 2;7. Epub 2018 Oct 2.

Epigenetics Programme, The Babraham Institute, Cambridge, United Kingdom.

Transcription of protein coding genes is accompanied by recruitment of COMPASS to promoter-proximal chromatin, which methylates histone H3 lysine 4 (H3K4) to form H3K4me1, H3K4me2 and H3K4me3. Here, we determine the importance of COMPASS in maintaining gene expression across lifespan in budding yeast. We find that COMPASS mutations reduce replicative lifespan and cause expression defects in almost 500 genes. Although H3K4 methylation is reported to act primarily in gene repression, particularly in yeast, repressive functions are progressively lost with age while hundreds of genes become dependent on H3K4me3 for full expression. Basal and inducible expression of these genes is also impaired in young cells lacking COMPASS components Swd1 or Spp1. Gene induction during ageing is associated with increasing promoter H3K4me3, but H3K4me3 also accumulates in non-promoter regions and the ribosomal DNA. Our results provide clear evidence that H3K4me3 is required to maintain normal expression of many genes across organismal lifespan.
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http://dx.doi.org/10.7554/eLife.34081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168286PMC
October 2018

Host lipidome analysis during rhinovirus replication in HBECs identifies potential therapeutic targets.

J Lipid Res 2018 09 26;59(9):1671-1684. Epub 2018 Jun 26.

Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, United Kingdom

In patients with asthma or chronic obstructive pulmonary disease, rhinovirus (RV) infections can provoke acute worsening of disease, and limited treatment options exist. Viral replication in the host cell induces significant remodeling of intracellular membranes, but few studies have explored this mechanistically or as a therapeutic opportunity. We performed unbiased lipidomic analysis on human bronchial epithelial cells infected over a 6 h period with the RV-A1b strain of RV to determine changes in 493 distinct lipid species. Through pathway and network analysis, we identified temporal changes in the apparent activities of a number of lipid metabolizing and signaling enzymes. In particular, analysis highlighted FA synthesis and ceramide metabolism as potential anti-rhinoviral targets. To validate the importance of these enzymes in viral replication, we explored the effects of commercially available enzyme inhibitors upon RV-A1b infection and replication. Ceranib-1, D609, and C75 were the most potent inhibitors, which confirmed that FAS and ceramidase are potential inhibitory targets in rhinoviral infections. More broadly, this study demonstrates the potential of lipidomics and pathway analysis to identify novel targets to treat human disorders.
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http://dx.doi.org/10.1194/jlr.M085910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121942PMC
September 2018