Activation-induced cytidine deaminase, an antibody diversification enzyme, interacts with chromatin modifier UBN1 in B-cells

Abstract

Abstract Activation-induced cytidine deaminase (AID) is the key mediator of antibody diversification in activated B-cells by the process of somatic hypermutation (SHM) and class switch recombination (CSR). Targeting of AID to the Ig genes requires transcription (initiation and elongation), and enhancers as well as its interaction with numerous factors. Furthermore, the HIRA chaperone complex, a regulator of chromatin architecture, is indispensable for SHM. The HIRA chaperone complex consists of UBN1, ASF1a, HIRA, and CABIN1 that deposit H3.3 onto the DNA, which is a hallmark of SHM. We explored whether UBN1 interacts with AID using computational as well as in-vitro experiments. Interestingly, our in-silico studies, such as molecular docking and molecular dynamics simulation results, predict that AID interacts with UBN1. Subsequent co-immunoprecipitation experiments established interactions between UBN1 and AID inside B-cells. Additionally, a double immunofluorescence assay confirmed that AID and UBN1 were co-localized in the human as well as chicken B-cell lines. Moreover, proximity ligation assay studies validated that AID interacts with UBN1. Ours is the first report on the interaction of genome mutator enzyme AID with UBN1. Nevertheless, the fate of interaction between UBN1 and AID is yet to be explored in the context of SHM or CSR.