Rabbit Anti-Human RNF20 (C-terminal) Polyclonal antibody

Overcoming the cellular type I interferon (IFN) host defense response is critical for a virus to ensure successful infection. Investigating the effects of human adenovirus (HAdV) infection on global cellular histone posttranslational modification (hPTM), we discovered that virus infection-induced activation of IFN signaling triggers a global increase in the monoubiquitination of histone 2B (H2B) at lysine 120, which is a mark for transcriptionally active chromatin. This hPTM, catalyzed by the hBre1/RNF20 complex, is necessary for activation of the cellular IFN-stimulated gene (ISG) expression program in response to viruses. To establish effective infection, the HAdV El A protein binds to and dissociates the hBre1 complex to block IFN-induced H2B monoubiquitination and associated ISG expression. Together, these data uncover a key role for H2B monoubiquitination in the type I IFN response and a viral mechanism of antagonizing this hPTM to evade the IFN response.

Post-translational modifications (PTMs) of histones are crucial for transcriptional control, defining positive and negative chromatin territories. A switch of opposing functional significance between acetylation and methylation occurs on many residues. Lysine 120 of H2B is modified by two PTMs: ubiquitination, which is required for further trans-tail H3 methylations and elongation, and acetylation, whose role is less clear. ChIP-Seq with MNase I-treated chromatin indicates that H2BK120ac is present on nucleosomes immediately surrounding the TSS of transcribed or poised units, but not in core promoters. In kinetic ChIP analysis of ER-stress inducible genes, H2BK120ac precedes activation and H2B-ub deposition. Using in vitro acetylation assays, pharmacologic inhibition and RNAi, we established that KAT3 is responsible for H2BK120ac. Interestingly, the global levels of H2B-ub decreased in KAT3-inactivated cells. However, RNF20 recruitment was not impaired by KAT3-inactivation. Our data point at acetylation of Lysine 120 of H2B as an early mark of poised or active state and establish a temporal sequence between acetylation and mono-ubiquitination of this H2B residue.