We revealed that, in response to viral infection, ARID1A can be recruited by IRF3 at the Ifn-I promoters and interact with the protein methyltransferase NSD2 which methylates H3K4 (H3K4Me3) and H3K36 (H3K36Me2) to facilitate chromatin accessibility at the Ifn-I promoters, resulting in the increased transcription of Ifn-I. This evidence concerns the gene IRF3 and viral infectious disease.