USP22 controls type III interferon signaling and SARS-CoV-2 infection through activation of STING

Within the context of the DUB module in the SAGA complex, USP22 is involved in transcriptional elongation through the regulation of H2AK119ub1 and H2BK120ub1. However, up till now, the spectrum of USP22-regulated target genes largely remains unclear, partially due to organism-, cell- and context-dependent redundancy in alternative DUBs that might compensate for loss of USP22. To understand which genes are regulated by USP22, we profiled USP22-dependent changes in gene expression in the human intestinal epithelial cell (hIEC) line HT-29. The human intestinal epithelial cell line HT-29 was subjected to CRISPR/Cas9 mediated knockout of USP22 and control (non-human target: nht), followed by single clone selection and confirmation of the knockout using Western blot. Single clones X16 and X62 were cultivated in defined settings to ensure equal conditions.