Epigenomic Modifications Mediating Antibody Maturation

Emily C Sheppard; Rikke Brandstrup Morrish; Michael J Dillon; Rebecca Leyland; Richard Chahwan

doi:10.3389/fimmu.2018.00355

Epigenomic Modifications Mediating Antibody Maturation

Emily C Sheppard, Rikke Brandstrup Morrish, Michael J Dillon, Rebecca Leyland, Richard Chahwan

Research output: Contribution to journal › Review article › peer-review

24 Citations (Scopus)

30 Downloads (Pure)

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.

Original language	English
Article number	355
Number of pages	15
Journal	Frontiers in Immunology
Volume	9
DOIs	https://doi.org/10.3389/fimmu.2018.00355
Publication status	Published - Mar 2018
Externally published	Yes

Keywords

Animals
Chromatin/genetics
Cytidine Deaminase/metabolism
DNA Repair
Epigenesis, Genetic
Histones/metabolism
Humans
Immune System Diseases/genetics
Immunity, Humoral
Immunoglobulin Class Switching
Neoplasms/genetics
RNA, Untranslated/genetics
Somatic Hypermutation, Immunoglobulin

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Epigenomic Modifications Mediating Antibody Maturation
Copyright © 2018 The Authors. open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
Final published version, 993 KBLicence: CC BY

Cite this

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title = "Epigenomic Modifications Mediating Antibody Maturation",

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.",

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author = "Sheppard, {Emily C} and Morrish, {Rikke Brandstrup} and Dillon, {Michael J} and Rebecca Leyland and Richard Chahwan",

year = "2018",

month = mar,

doi = "10.3389/fimmu.2018.00355",

language = "English",

volume = "9",

journal = "Frontiers in Immunology",

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publisher = "Frontiers Media S.A.",

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TY - JOUR

T1 - Epigenomic Modifications Mediating Antibody Maturation

AU - Sheppard, Emily C

AU - Morrish, Rikke Brandstrup

AU - Dillon, Michael J

AU - Leyland, Rebecca

AU - Chahwan, Richard

PY - 2018/3

Y1 - 2018/3

N2 - 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.

AB - 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.

KW - Animals

KW - Chromatin/genetics

KW - Cytidine Deaminase/metabolism

KW - DNA Repair

KW - Epigenesis, Genetic

KW - Histones/metabolism

KW - Humans

KW - Immune System Diseases/genetics

KW - Immunity, Humoral

KW - Immunoglobulin Class Switching

KW - Neoplasms/genetics

KW - RNA, Untranslated/genetics

KW - Somatic Hypermutation, Immunoglobulin

U2 - 10.3389/fimmu.2018.00355

DO - 10.3389/fimmu.2018.00355

M3 - Review article

C2 - 29535729

SN - 1664-3224

VL - 9

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 355

ER -

Epigenomic Modifications Mediating Antibody Maturation

Abstract

Keywords

UN SDGs

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