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Fig. 7 | Journal of Translational Medicine

Fig. 7

From: Chronic loss of STAG2 leads to altered chromatin structure contributing to de-regulated transcription in AML

Fig. 7

Pathway analysis identifies MAPK signalling as a potential therapeutic target in ΔSTAG2 cells. a Ingenuity Pathway Analysis (IPA) network diagram displaying altered expression of MAPK signaling related genes in ΔSTAG2 cells. Genes whose expression was increased or decreased in Δ STAG2 cells are highlighted in red and green respectively. b Fold change in expression of genes specifically identified in the IPA MAPK signaling network generated from normalized RNA-Seq read counts in STGA2-WT and ΔSTAG2 cells. c Virtual 4C plot displaying interactions over a 600 kb region of chromosome 8 encompassing the DUSP4 gene. The V4c plot is anchored upstream of the DUSP4 gene. d Virtual 4C plot displaying interactions over a 600 kb region of chromosome 8 encompassing the ZEB1 gene. The V4c plot is anchored upstream of the ZEB1 gene. e, f Dose response assay displaying increased sensitivity of ΔSTAG2 cells compared to STAG2-WT cells to the MEKi Selumetinib (e) and Trametinib (f). Cell death was assessed 24-h following treatment using the cell titre-glow assay as a readout. Cellular survival in plotted as a percentage signal normalised to control/vehicle treated cells. g Representative Western Blot showing lower dose Selumetinib mediated inhibition of ERK1/2 phosphorylation and induction of apoptosis (indicated by PARP and Caspase 3 cleavage) in ΔSTAG2 cells compared to the STAG2-WT cells. Densitometry analysis of this blot is shown in Additional file 1: Figure S4D–F

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