Extended Data Fig. 7: Inhibition of KDM5 induces TSS switching that remodels 5´UTRs and is associated with proteome changes.
From: Epigenetic alterations facilitate transcriptional and translational programs in hypoxia
a, PCA of 5´UTR isoform expression measured by nanoCAGE sequencing in T47D cells treated with 10 μM C48 for 24 h, and DMSO-treated controls (n = 4 independent experiments). b, Kernel density estimation change-point TSS switch score distributions for transcripts with significant (FDR < 0.15) TSS switching after C48 treatment (n = 3,287), compared to hypoxia in T47D cells (n = 2,552). Higher values indicate greater differences in 5´UTR isoform expression. c,d, PCA of GPF-DIA proteomics data (c), and mRNA expression measured by RNA-seq (d) in T47D cells treated with 10 μM C48 for 24 h, and DMSO-treated controls (n = 4 independent experiments). e, Gene ontology enrichments for genes where protein levels were altered independent of changes in mRNA levels in C48-treated T47D cells. f, PCA of 5´UTR isoform expression measured by nanoCAGE sequencing in T47D cells co-treated with hypoxia and either 25 µM OICR-9429 or DMSO vehicle control (n = 3 independent experiments). g, Gene ontology enrichments for genes where hypoxia-induced TSS switching was reversed by OICR-9429 treatment. Source numerical data are available in.
