Fig. 4: CBP-1 links VHA-6 loss to LySR activation and longevity.
From: A lysosomal surveillance response to stress extends healthspan
a, All the KATs in C. elegans and their human homologues. b, The identification of CBP-1 as an essential gene for LySR activation. cpr-5p::gfp worms were treated with control (ev) or vha-6 (25%) RNAi in combination with RNAi targeting different KATs (75%). Scale bar, 0.3 mm. c, A shematic diagram showing the different regions targeted by the two different cbp-1 RNAi clones. KIX, kinase-inducible domain interacting domain; Br, bromodomain; HAT, histone acetyltransferase domain; a.a., amino acids; nt, nucleotides. d, A qRT–PCR analysis (n = 4 biologically independent samples) of worms treated with control, cbp-1 and/or vha-6 RNAi (****P < 0.0001; for cpr-5, **P = 0.0091 (ev versus cbp-1_1), **P = 0.0092 (ev versus cbp-1_2); for cpr-8, *P = 0.0315 (ev versus cbp-1_1), *P = 0.0368 (ev versus cbp-1_2); for ctsa-1, P = 0.6009 (not significant (n.s.), ev versus cbp-1_1), P = 0.6595 (n.s., ev versus cbp-1_2); for asp-10, P = 0.9997 (n.s., ev versus cbp-1_1), P = 0.9995 (n.s., ev versus cbp-1_2); for vha-6, **P = 0.0066 (vha-6 versus vha-6 + cbp-1_1), **P = 0.0100 (vha-6 versus vha-6 + cbp-1_2); for cbp-1, **P = 0.0025 (ev versus cbp-1_2), ***P = 0.0001 (vha-6 versus vha-6 + cbp-1_1), *P = 0.0206 (vha-6 versus vha-6 + cbp-1_2)). e, H3K27 acetylation increases in a CBP-1-dependent manner during LySR activation induced by vha-6 RNAi. The worms were treated with control, cbp-1 RNAi_1 and/or vha-6 RNAi. f, A ChIP–qPCR (n = 4 biologically independent samples) of elt-2p::elt-2::gfp-flag worms treated with control, vha-6 and/or cbp-1 RNAi_1 (****P < 0.0001). IP, immunoprecipitation. g, The survival of worms treated with control, vha-6 (20%), and/or cbp-1 (50%) RNAi_1 (****P < 0.0001, *P = 0.0102 (cbp-1 versus vha-6 + cbp-1)). The error bars denote the standard error of the mean. The statistical analysis was performed by ANOVA followed by Tukey’s post hoc test in d and f or a log-rank test in g. The statistical data for lifespan can be found in Supplementary Table 1.
