fig3

Figure 3. Ectopic HIF2A is associated with less DNA damage. (A) Gene ontology analysis by Gorilla algorithm shows pathways that are significantly upregulated in MCM;HIF2A-OE relative to control hearts. Reg/of: Regulation of; NT: nucleotide; ROS: reactive oxygen species; Org: organic; OH: hydroxy; cat: catabolic. (B) Gene Set Enrichment Analysis (GSEA) shows that pathways associated with DNA damage and repair are upregulated in the control hearts. Zero cross is at 9014. Top: non-homologous end-joining (NHEJ) and bottom: DNA double-strand break response. EF: Enrichment score. (C-G) Quantification and immunoblots of DNA damage-associated proteins in control and MCM;HIF2A-OE hearts. (H and I) Representative immunofluorescent stained cardiac tissue sections and quantification of 8-oxoG nuclei from control and MCM;HIF2A-OE hearts. (J) Proposed schematic for HIF2A mechanism in CMs (created with BioRender.com.) OE: Overexpression; NHEJ: non-homologous end-joining; dsDNA: double stranded DNA; ES: enrichment score.