Fig 2: ARID1A interacts with NSD2 to promote methylation of Ifn-I promoters.A Co-IP analysis of the interaction between endogenous ARID1A and NSD2 in macrophages. B Immunofluorescence of ARID1A and NSD2 localization in macrophages (scale bar: 10 µm). C Co-IP analysis of the interaction between tagged ARID1A and tagged wild type NSD2 or indicated NSD2 mutants in HEK293T cells. D Co-IP analysis of the interaction between tagged IRF3 and tagged wild type NSD2 or indicated NSD2 mutants in HEK293T cells. E–F ChIP assay of H3K4Me3 and H3K36Me2 in the Ifnb (E) and Ifna (F) promoter regions of Arid1a f/f Lyz-Cre- and Arid1a f/f Lyz-Cre+ BMDMs with VSV infection (MOI, 1) at the indicated times. G, H ChIP assay of H3K4Me3 and H3K36Me2 in the Tnfa (G) and Il6 (H) promoter regions of cells as in (E–F). All data are representative of three independent experiments with three biological replicates. *P < 0.05, **P < 0.01. (E–H: mean ± s.d.).

Fig 3: NSD2 promotes IFN-I production by mediating histone methylation of Ifn-I promoters.A, B qPCR analysis of Ifn-I (A) and ELISA analysis of IFN-I (B) expression in Arid1a f/f Lyz-Cre- and Arid1a f/f Lyz-Cre+ BMDMs transfected with wild type Arid1a and Arid1a-?ARID construct and then infected with VSV (MOI, 1) at the indicated times, mock served as control. C, D qPCR analysis of Ifn-I (C) and ELISA analysis of IFN-I (D) expression in Arid1a f/f Lyz-Cre- and Arid1a f/f Lyz-Cre+ BMDMs transfected with wild type Nsd2 or Nsd2-?SET construct and then infected with VSV (MOI, 1) at the indicated times, mock served as control. E, F ChIP assay of H3K4Me3 and H3K36Me2 in the Ifnb (E) or Ifna (F) promoter regions of Arid1a f/f Lyz-Cre- and Arid1a f/f Lyz-Cre+ BMDMs transfected with plasmids as in (C–D) in response to VSV (MOI, 1) infection at the indicated times. Error bars represent s.d. Student’s t-test. *P < 0.05, **P < 0.01, ***P < 0.001. All data are representative of three independent experiments with three biological replicates. (A–F: mean ± s.d.).