Fig. 5

H3K27 acetylation is associated with the relative proportion of p300 and non-SIRT1 HDAC binding and overrepresented in PD-implicated genes. a, b Examples of two PD_implicated genes, SNCA (a) and VPS35 (b). SNCA harbors a DAR (Peak_35531/27168 in PW/NBB respectively) in an enhancer element whose H3K27 acetylation status is associated with both genetic variation (SNP rs356168) and drugs influencing the risk of PD. VPS35 does not exhibit DARs in our data. Purple bars indicate H3K27ac peaks in the PW and NBB peaksets. H3K27ac ChIP-seq data from ENCODE is shown for reference. Pink, blue and yellow bars indicate the binding sites of p300, HDAC1 and HDAC2 respectively, based on ENCODE ChiP-seq data wgEncodeRegTfbsClusteredV3.bed. c, d Difference in the relative number of p300 and non-SIRT1 HDAC bindings sites between significantly hyperacetylated and non-significantly hyperacetylated peaks for all (c, Kolmogorov–Smirnov test) or only PD_implicated (d, two-sided Wilcoxon rank sum test) genes. e Hyperacetylated – regions showing hyperacetylation in both cohorts; Mixed – regions with opposite acetylation trends in the two cohorts. The dashed line represents the -log10 of the highest metaP corresponding to adjusted metaP < 0.05. Multiple common regions within the same gene are shown. Highlighted are regions identified as DAR in at least one of the cohorts within PD-implicated genes. metaP – Fisher’s meta-p value of the corresponding two peaks from PW and NBB cohorts. f Association between -log(p) and each of the indicated covariates based on linear model. Shown are the coefficients and 95% confidence intervals. The results are shown for the common regions (metaP) and each of the cohorts separately. Peaks annotated to miRNAs and snRNAs were excluded from the analysis. PDgene – a gene is a PD-implicated gene. EGL – effective gene length. TotalPeaks – total number of common regions or peaks annotated to the gene