The KDM6A-KMT2D-p300 axis regulates susceptibility to diverse coronaviruses by mediating viral receptor expression
Fig 2
KDM6A regulates ACE2 and DPP4 expression in a demethylase-independent manner.
(A-B) ACE2 and DPP4 expression in KDM6A KO Vero E6 cells at mRNA level (A) and protein level (B). (C-D) VSVpp- based pseudovirus entry in WT Vero E6 cells and KDM6A KO cells rescued with either human ACE2 (C) or human DPP4 (D). (E) Schematic of full length KDM6A and its mutants. (F) Immunoblot for ACE2 and KDM6A in KDM6A rescued cells. (G) KDM6A KO rescued cells were infected with icSARS-CoV-2-mNG at an MOI of 1. Infected cells were imaged via fluorescence microscopy (left) and mNeonGreen expressing cell frequency was measured 2 dpi (right). Scale bar: 300 μm. (H) KDM6A KO rescued Vero E6 cells were infected with VSV pseudovirus (VSVpp): VSV-G, SARS-CoV-2-S (left), SARS-CoV-S (middle), and MERS-CoV-S (right). Luciferase relative to the VSVpp-VSV-G control was measured 1 dpi. Data were analyzed by one-way ANOVA with Tukey’s multiple comparison test. Shown are mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001.