Figure 2.

Crosstalk and antagonism between GC and canonical Wnt signaling. (A) CUT&RUN sequencing read enrichment at LEF1 binding sites ± 1 kb (cell signaling antibody #2230). Enrichment is shown for a 24-hour treatment with vehicle control (left) or prednisolone (5 μM; GC) (right). (B) Log₂-transformed normalized CUT&RUN sequencing read counts at LEF1 binding sites treated for 24 hours with vehicle control (x-axis) or prednisolone (y-axis). Binding sites exhibiting significant differences in occupancy (false discovery rate <0.05) are shown in pink. (C) Integrative Genomics Viewer (IGV) genome browser images of signal tracks providing examples of GR and LEF1 co-occupancy at BCL6 (left) and BMF (right) gene loci. (D) Log₂-transformed fold changes of genes commonly regulated by GC and Wnt signaling pathways in Nalm6 cells after 24 hours of treatment using 5 μM prednisolone (GC-response genes; x-axis) or 0.5 μM CHIR-99021 (Wnt-response genes; y-axis). GC-response and Wnt-response gene log₂ fold changes are provided. The percentage of genes in each quadrant is provided, and genes showing opposing effects are highlighted in quadrants 2 and 4. Red denotes genes involved in cell death, cell proliferation, and/or cell cycle pathways and notable genes are labeled. (E) Log₂-transformed fold changes of genes commonly regulated by GC and Wnt signaling pathways in Nalm6 cells after 24 hours of treatment using 100 nM dexamethasone (GC-response genes; x-axis) or 0.5 μM CHIR-99021 (Wnt-response genes; y-axis). GC-response and Wnt-response gene log₂ fold changes are provided. The percentage of genes in each quadrant is provided, and genes showing opposing effects are highlighted in quadrants 2 and 4. Red denotes genes involved in cell death, cell proliferation, and/or cell cycle pathways and notable genes are labeled. (F) Volcano plot of differential protein expression between prednisolone (5 μM) or CHIR-99021 (0.5 μM) treatment for 24 hours. Plot shows proteins of discordantly regulated prednisolone-response and Wnt-response genes with consistent directionality. Red denotes proteins involved in cell death, cell proliferation, and/or cell cycle pathways, and notable proteins are labeled.