Fig. 3: Acetylation site mutant of MED1 alters steady-state and stress-responsive gene expression in ER+ BC cells.
From: MED1 IDR deacetylation controls stress responsive genes through RNA Pol II recruitment
a, GSEA showing that the upregulated (left) and downregulated (right) genes in 6KR/KO versus WT/KO cells were enriched in the set of downregulated and upregulated genes of MED1-KO (versus control) cells, respectively. The cutoff for defining DEGs was fold change (FC) > 2 and adjusted P < 0.05. NES (normalized enrichment score) values are shown. b,c, Detection by RT–qPCR showing stronger induction of representative stress-induced genes in 6KR/KO versus WT/KO MCF7 cells. b, Genes induced by DFOM. c, Genes induced 42 °C heat shock for 60 or 120 min. For each of WT/KO or 6KR/KO cells, expression of the gene at each condition was normalized by its expression at control condition in this cell type. For b,c, n = 4 (biological replicates) for each group. Bars report the mean ± s.e.m. If <0.05, the P values of a two-sided unpaired t-test comparing cell types are shown. d–i, Poly(A) RNA-seq for MCF7 cells under H2O2 stress, comparing 6KR/KO versus WT/KO or 6KQ/KO versus WT/KO. Three biological replicates were detected for each cell type in each condition. d, Volcano plots showing the log2 FC versus Wald statistics (two-sided) after H2O2 treatment for each detected gene in tests of WT/KO, 6KR/KO and 6KQ/KO cells, with the cutoff for defining DEGs (FC > 2, P < 0.05) indicated. e, A clustered heat map of z scores of genes showing differential expression by H2O2 treatment (adjusted P < 0.05) in any of the WT/KO, 6KR/KO or 6KQ/KO cells. A division of six groups for these genes is shown. Colors in the scale represent relative expression levels: blue (z ≤ −3), white (z = 0), and red (Z ≥ 3), with a linear gradient for intermediate values. f, A box plot showing the FC by H2O2 treatment for group B genes (n = 1,601) in WT/KO, 6KR/KO and 6KQ/KO cells. g, FC values (H2O2 treatment versus control condition in each cell type) of representative stress-protective genes in group B. If <0.05, the P values from a two-sided unpaired t-test are shown. h, A box plot showing FC by H2O2 treatment for group F genes (n = 8481) in WT/KO, 6KR/KO and 6KQ/KO cells. i, GO analyses with adjusted P values for GOBP (left) and KEGG (right) gene lists for group F genes. For f,h, boxes span the 25th–75th percentiles, the center line indicates the median, whiskers extend to 1.5× the interquartile range (IQR) and points beyond represent outliers. P values of a two-sided unpaired t-test comparing cell types are shown.
