Epigenomic modifications mediating antibody maturation

SHEPPARD, Emily C, MORRISH, Rikke Brandstrup, DILLON, Michael J, LEYLAND, Rebecca and CHAHWAN, Richard (2018). Epigenomic modifications mediating antibody maturation. Frontiers in immunology, 9, p. 355.

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Official URL: https://www.frontiersin.org/articles/10.3389/fimmu...
Link to published version:: https://doi.org/10.3389/fimmu.2018.00355

Abstract

Epigenetic modifications, such as histone modifications, DNA methylation status, and non-coding RNAs (ncRNA), all contribute to antibody maturation during somatic hypermutation (SHM) and class-switch recombination (CSR). Histone modifications alter the chromatin landscape and, together with DNA primary and tertiary structures, they help recruit Activation-Induced Cytidine Deaminase (AID) to the immunoglobulin (Ig) locus. AID is a potent DNA mutator, which catalyzes cytosine-to-uracil deamination on single-stranded DNA to create U:G mismatches. It has been shown that alternate chromatin modifications, in concert with ncRNAs and potentially DNA methylation, regulate AID recruitment and stabilize DNA repair factors. We, hereby, assess the combination of these distinct modifications and discuss how they contribute to initiating differential DNA repair pathways at the Ig locus, which ultimately leads to enhanced antibody-antigen binding affinity (SHM) or antibody isotype switching (CSR). We will also highlight how misregulation of epigenomic regulation during DNA repair can compromise antibody development and lead to a number of immunological syndromes and cancer.

Item Type: Article
Additional Information: ** From PubMed via Jisc Publications Router. ** History: received 27-11-2017; accepted 08-02-2018.
Uncontrolled Keywords: B cell maturation, antibody diversity, class-switch recombination, cytosine deamination, epigenetic modifications, epigenomics and epigenetics, somatic hypermutation
Departments: Health and Well-being > Bioscience
Identification Number: https://doi.org/10.3389/fimmu.2018.00355
SWORD Depositor: Margaret Boot
Depositing User: Margaret Boot
Date Deposited: 27 Mar 2018 09:13
Last Modified: 27 Mar 2018 22:31
URI: http://shura.shu.ac.uk/id/eprint/19026

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