Fig. 6: FOS transcription is differentially regulated by p30/p42 and partially explains the reduced inflammatory expression.
From: Mutant CEBPA promotes tolerance to inflammatory stress through deficient AP-1 activation
a Differential gene expression of FOS subfamily members in various experimental models: CEBPAbi/NT -mutated AML compared to all the other AML subtypes, p30 vs p42 HPC-7 cells, CebpaFl/p30;R26-CreER (p30) macrophages versus CebpaFl/Fl (WT) macrophages, and in CebpaFl/p30;R26-CreER (p30) vs CebpaFl/Fl (WT) bone marrow (BM) hematopoietic progenitors. b Log2 fold-change of gene expression of FOS subfamily members in each AML mutant compared to the rest of AML patients WT for that particular mutation. c FOS expression (normalized counts at log2 scale) in AML patients with wild-type CEBPA (n = 759), CEBPA C-terminal mutations (n = 17) or biallelic and N-terminal CEBPA mutations (n = 32). d Correlation of FOS and CEBPA gene expression in AML cell lines from DepMap65. e Ratio of FOS/CEBPA gene expression in CEBPA-mutant (n = 2) and wild-type (n = 18) AML cell lines. Linear regression with standard error. f Virtual 4 C of the Fos gene locus in p42 and p30-expressing HPC-7 cells. Tracks: ChiP-seq of p42 (blue) and p30 (red); ChIP-seq of H3K27ac in p42 (blue) and p30 (red) expressing cells. g Expression (z-score) of inflammatory genes in AML patients stratified by FOS expression. Low and high represent the bottom and top 50 patients by FOS expression, respectively. h Quantitative RT-PCR of representative inflammatory genes in KO-52 cells transduced with FOS, expression relative to an empty vector control (dotted line) and normalized to HPRT and RPL38. In blue, downregulated genes; in red, upregulated (p value < 0.05) and in gray, non-significant changes (p value > 0.05), two-tailed unpaired t test; mean ± SEM, n = 3 biological replicates. c, e, g Boxplots center lines represent the median, lower and upper hinges correspond to the first and third quartiles (25th and 75th percentiles). Upper whisker extends from the hinge to the largest value no further than 1.5 * IQR from the hinge (IQR, inter-quartile range). Lower whisker extends from the hinge to the smallest value at most 1.5 * IQR of the hinge. Source data are provided as a Source Data file.
