Fig. 7: SET-26 and HCF-1 control expression of a subset of genes which are co-regulated by HDA-1 in an antagonistic manner. | Nature Communications

Fig. 7: SET-26 and HCF-1 control expression of a subset of genes which are co-regulated by HDA-1 in an antagonistic manner.

From: The chromatin factors SET-26 and HCF-1 oppose the histone deacetylase HDA-1 in longevity and gene regulation in C. elegans

Fig. 7

a Heatmap showing hierarchical clustering of HDA-1-dependent genes identified as differentially expressed with hda-1 RNAi during aging in either day 12 adult glp-1(-);set-26(-) or glp-1(-);hcf-1(-) worms but not glp-1(-) single mutants. Log2 fold change of RNA expression for these genes in day 12 samples are indicated by color. Columns 1–2 show expression changes in glp-1(-);set-26(-) or glp-1(-);hcf-1(-) vs glp-1(-), and columns 3–4 show expression changes in glp-1(-);set-26(-) or glp-1(-);hcf-1(-) on hda-1 RNAi vs E.V. during aging. The heatmap is split into three hierarchical clusters representing different behaviors. b, c Wormcat enrichment analysis of cluster 1 or 3. Wormcat p values are determined by one-sided Fisher test with FDR correction. d Heatmap showing hierarchical clustering of direct somatic binding targets of SET-26, HCF-1, and HDA-1 that were also identified by ref. 13 as “HDA-1-dependent mitoUPR genes”. Log2 fold change of these genes in our day 12 data set are shown by color. As above, columns 1-2 show expression changes in germline-less set-26(-) and hcf-1(-) mutants vs controls, and columns 3–4 show the expression change in germline-less set-26(-) and hcf-1(-) mutants on hda-1 RNAi vs E.V. during aging. e Venn diagram showing overlap of the common CUT&RUN targets of SET-26, HCF-1, and HDA-1 that are also “HDA-1-dependent mitoUPR genes” as indicated in (d) with the 122 genes on which somatic SET-26 and HCF-1 binding stabilize each other and show higher RNA expression in both mutants as identified in Fig. 4h. f The proposed model, in which SET-26 recruits HCF-1 to chromatin, HCF-1 stabilizes SET-26, and the pair work together to regulate gene expression. The model proposes that HDA-1 co-regulates a subset of genes with SET-26 and HCF-1, often mitochondrial and lipid metabolism genes, but in the opposite direction. Together, the factors contribute to the balance of gene regulation and longevity. In (e), *** indicates p < 1 × 10−15 and the overlap is higher than expected by chance, as calculated by one-sided Fisher’s Test. Gene sets are provided in Supplementary Data 3. N = 2 for RNA-seq.

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