Figure 7.

Acute and chronic changes to cancer and stem cell signaling following loss of ARID1A

(A) Illustration of the two pathways by which ARID1A and EP300 act in upregulation and downregulation of gene expression. At sites adjacent to downregulated genes, chromatin accessibility (orange dots) and EP300 occupancy (blue dots) are reduced. In contrast, upregulated genes are linked to loss of EP300 occupancy in the absence of chromatin changes. These changes are enriched at genes that change expression after 2 h. Changes in expression are detected at many more genes in subsequent hours and days, but not mechanistically linked to loss of ARID1A.

(B) The top pathways enriched following chronic ARID1A loss are illustrated together with the progressive engagement with these pathways over time, indicated by −log₁₀ p values.

(C) Genes associated with the pathways indicated that change (FDR < 0.05, fold change > log₂ 0.5-fold) up to 6 h following loss of ARID1A are indicated together with the log₂ transcriptional changes at all time points. The early changing components of these pathways are likely to drive downstream changes that propagate further engagement with pathways. Several early changing regulators contribute to multiple pathways. This suggests that changes to transcription of a small number of genes drives engagement with the biological pathways that shape the ARID1A^−/− phenotype.