Activation-induced cytidine deaminase an antibody diversification enzyme interacts with chromatin modifier UBN1 in B-cells
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 AID to the Ig genes requires transcription (initiation and elongation), enhancers, a...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-46448-7 |
| _version_ | 1797630246014418944 |
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| author | Ankit Jaiswal Rajarshi Roy Anubhav Tamrakar Amit Kumar Singh Parimal Kar Prashant Kodgire |
| author_facet | Ankit Jaiswal Rajarshi Roy Anubhav Tamrakar Amit Kumar Singh Parimal Kar Prashant Kodgire |
| author_sort | Ankit Jaiswal |
| collection | DOAJ |
| description | 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 AID to the Ig genes requires transcription (initiation and elongation), enhancers, and its interaction with numerous factors. Furthermore, the HIRA chaperon complex, a regulator of chromatin architecture, is indispensable for SHM. The HIRA chaperon complex consists of UBN1, ASF1a, HIRA, and CABIN1 that deposit H3.3 onto the DNA, the SHM hallmark. We explored whether UBN1 interacts with AID using computational and in-vitro experiments. Interestingly, our in-silico studies, such as molecular docking and molecular dynamics simulation results, predict that AID interacts with UBN1. Subsequently, co-immunoprecipitation and pull-down 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 and 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. |
| first_indexed | 2024-03-11T11:05:31Z |
| format | Article |
| id | doaj.art-893d78a10031416283f8d7dfa4b726c3 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-11T11:05:31Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-893d78a10031416283f8d7dfa4b726c32023-11-12T12:15:29ZengNature PortfolioScientific Reports2045-23222023-11-0113111310.1038/s41598-023-46448-7Activation-induced cytidine deaminase an antibody diversification enzyme interacts with chromatin modifier UBN1 in B-cellsAnkit Jaiswal0Rajarshi Roy1Anubhav Tamrakar2Amit Kumar Singh3Parimal Kar4Prashant Kodgire5Department of Biosciences and Biomedical Engineering, Indian Institute of TechnologyDepartment of Biosciences and Biomedical Engineering, Indian Institute of TechnologyDepartment of Biosciences and Biomedical Engineering, Indian Institute of TechnologyDepartment of Biosciences and Biomedical Engineering, Indian Institute of TechnologyDepartment of Biosciences and Biomedical Engineering, Indian Institute of TechnologyDepartment of Biosciences and Biomedical Engineering, Indian Institute of TechnologyAbstract 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 AID to the Ig genes requires transcription (initiation and elongation), enhancers, and its interaction with numerous factors. Furthermore, the HIRA chaperon complex, a regulator of chromatin architecture, is indispensable for SHM. The HIRA chaperon complex consists of UBN1, ASF1a, HIRA, and CABIN1 that deposit H3.3 onto the DNA, the SHM hallmark. We explored whether UBN1 interacts with AID using computational and in-vitro experiments. Interestingly, our in-silico studies, such as molecular docking and molecular dynamics simulation results, predict that AID interacts with UBN1. Subsequently, co-immunoprecipitation and pull-down 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 and 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.https://doi.org/10.1038/s41598-023-46448-7 |
| spellingShingle | Ankit Jaiswal Rajarshi Roy Anubhav Tamrakar Amit Kumar Singh Parimal Kar Prashant Kodgire Activation-induced cytidine deaminase an antibody diversification enzyme interacts with chromatin modifier UBN1 in B-cells Scientific Reports |
| title | Activation-induced cytidine deaminase an antibody diversification enzyme interacts with chromatin modifier UBN1 in B-cells |
| title_full | Activation-induced cytidine deaminase an antibody diversification enzyme interacts with chromatin modifier UBN1 in B-cells |
| title_fullStr | Activation-induced cytidine deaminase an antibody diversification enzyme interacts with chromatin modifier UBN1 in B-cells |
| title_full_unstemmed | Activation-induced cytidine deaminase an antibody diversification enzyme interacts with chromatin modifier UBN1 in B-cells |
| title_short | Activation-induced cytidine deaminase an antibody diversification enzyme interacts with chromatin modifier UBN1 in B-cells |
| title_sort | activation induced cytidine deaminase an antibody diversification enzyme interacts with chromatin modifier ubn1 in b cells |
| url | https://doi.org/10.1038/s41598-023-46448-7 |
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