Tri-methylation of histone H3 lysine 4 facilitates gene expression in ageing cells
- The Babraham Institute, United Kingdom
Figures
Figure 1 with 2 supplements
The ageing transcriptome in wild type and COMPASS mutants.
(A) Schematic of COMPASS recruitment for deposition of H3K4me3. (B) Viability of mother cells after 48 hr in liquid YPD culture determined using the MEP system. p-values calculated by Kruskal-Wallis …
Figure 1—figure supplement 1
Supplement to the ageing transcriptome in wild type and COMPASS mutants.
(A) Viability of mother cells across 72 hr in liquid YPD culture using the MEP system for wild type and swd1Δ mutants. p-value calculated based on area under curve n = 5 for wild type, n = 3 for swd1…
Figure 1—figure supplement 2
Age-linked changes in gene expression profile.
(A) Hierarchical clustering analysis of log2-transformed protein-coding mRNA levels across ageing for the genes significantly differentially expressed between log phase and 48 hr in wild-type (left, …
Figure 2 with 1 supplement
COMPASS is required for normal gene expression in ageing cells.
(A) Plot of log2-transformed read-count differences for significantly differentially expressed genes between wild type and COMPASS mutants at each ageing time point. Assessed using DEseq2 p<0.01, …
Figure 2—figure supplement 1
Supplement to COMPASS is required for gene expression in ageing cells.
(A) Hierarchical clustering analysis of log2-transformed protein-coding mRNA levels across age for the 107 genes significantly differentially expressed between wild-type and COMPASS mutants at log …
Figure 3 with 2 supplements
Validation of gene expression differences in COMPASS mutants.
(A) Schematic representation of the regulatory feedback system controlling expression of the BNA genes which encode enzymes in the pathway for NAD+ biosynthesis from tryptophan via nicotinic acid …
Figure 3—figure supplement 1
Supplement to validation of gene expression differences in COMPASS mutants.
(A–F) Quantification of BNA gene induction by northern blot for BNA1, BNA6 and BNA7, performed as in Figure 3C.
Figure 3—figure supplement 2
Example northern blotting data.
(A,B) Example northern blots for BNA1 and BNA4-7 induction along with 18S signal visualised by ethidium staining. (C) Quantification of fold induction of BNA1 and BNA4-7 in the presence of 1 mM NIC …
Figure 4 with 2 supplements
Age-linked dynamics of H3K4me3.
(A) Violin plot of read counts for region from transcriptional start site (TSS) to TSS+ 500 bp for all genes lying outside excluded regions defined in Figure 4—figure supplement 1A and with …
Figure 4—figure supplement 1
Dynamics of H3K4me3 and expression in subsets of genes.
(A) Genomic regions subject to age-linked CNV detected by comparison between input samples; these were excluded from ChIP analysis. (B) Scatter plot of log2-transformed mRNAseq read counts from …
Figure 4—figure supplement 2
Age linked changes in genome size and H3 distribution
(A) Genome sizes in cells of different ages calculated using read counts of ChIP input samples, separated into rDNA and non-rDNA regions. (B) Average H3 density in 1 kb windows across rDNA and …
Figure 5
Predicted impacts of H3K4me2 and H3K4me3 on BNA gene expression.
Schematic of the different impacts of H3K4me2 and H3K4me3 on expression of the BNA genes analysed in Figure 3 and Figure 3—figure supplement 1. Depiction of these modifications on the +2 and+1 …
Author response image 1
Ratio of rRNA to ACT1 mRNA levels in wild-type cells across age.
https://doi.org/10.7554/eLife.34081.020Tables
Table 1
mRNAseq libraries analysed in this work.
https://doi.org/10.7554/eLife.34081.005Additional files
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Supplementary file 1
Supplementary Tables S1-S7.
S1: Summary of differentially expressed genes determined using DESeq2 S2: Regions of variable copy number excluded from ChIPseq analysis S3: Yeast strains used in this research S4: Oligonucleotides used in this research S5: Plasmids used in this research S6: Probes used in this research S7: Antibodies used in this research.
- https://doi.org/10.7554/eLife.34081.015
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Supplementary file 2
Full results of GO analyses Full output of GO analyses presented in Figure 1, Figure 1—figure supplement 1, Figure 2, Figure 2—figure supplement 1.
Only the Process Ontology is presented (as in the figures), the data here is the full output from GOrilla (cbl-gorilla.cs.technion.ac.il) with a P-value threshold of 0.001. However, only GO hits with an FDR-corrected q-value of <0.05 were considered significant in the final analysis.
- https://doi.org/10.7554/eLife.34081.016
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Supplementary file 3
Data underlying figures Numerical data used to produce all figures shown.
For hierarchical clustering diagrams, this includes the expression data and identifier for each gene.
- https://doi.org/10.7554/eLife.34081.017
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Transparent reporting form
- https://doi.org/10.7554/eLife.34081.018
