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Acetyltransferases GCN5 and PCAF Are Required for B Lymphocyte Maturation in Mice

B lymphocyte development has two DNA recombination processes: V(D)J recombination of the immunoglobulin (Igh) gene variable region, and class switching of the Igh constant regions from IgM to IgG, IgA, or IgE. V(D)J recombination is required for the successful maturation of B cells from pro-B to pre...

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Autores principales: Oksenych, Valentyn, Su, Dan, Daniel, Jeremy A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773862/
https://www.ncbi.nlm.nih.gov/pubmed/35053209
http://dx.doi.org/10.3390/biom12010061
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author Oksenych, Valentyn
Su, Dan
Daniel, Jeremy A.
author_facet Oksenych, Valentyn
Su, Dan
Daniel, Jeremy A.
author_sort Oksenych, Valentyn
collection PubMed
description B lymphocyte development has two DNA recombination processes: V(D)J recombination of the immunoglobulin (Igh) gene variable region, and class switching of the Igh constant regions from IgM to IgG, IgA, or IgE. V(D)J recombination is required for the successful maturation of B cells from pro-B to pre-B to immature-B and then to mature B cells in the bone marrow. CSR occurs outside of the bone marrow when mature B cells migrate to peripheral lymphoid organs, such as spleen and lymph nodes. Both V(D)J recombination and CSR depend on an open chromatin state that makes DNA accessible to specific enzymes, recombination activating gene (RAG), and activation-induced cytidine deaminase (AID). Acetyltransferases GCN5 and PCAF possess redundant functions acetylating histone H3 lysine 9 (H3K9). Here, we generated a mouse model that lacked both GCN5 and PCAF in B cells. Double-deficient mice possessed low levels of mature B cells in the bone marrow and peripheral organs, an accumulation of pro-B cells in bone marrow, and reduced CSR levels. We concluded that both GCN5 and PCAF are required for B-cell development in vivo.
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spelling pubmed-87738622022-01-21 Acetyltransferases GCN5 and PCAF Are Required for B Lymphocyte Maturation in Mice Oksenych, Valentyn Su, Dan Daniel, Jeremy A. Biomolecules Article B lymphocyte development has two DNA recombination processes: V(D)J recombination of the immunoglobulin (Igh) gene variable region, and class switching of the Igh constant regions from IgM to IgG, IgA, or IgE. V(D)J recombination is required for the successful maturation of B cells from pro-B to pre-B to immature-B and then to mature B cells in the bone marrow. CSR occurs outside of the bone marrow when mature B cells migrate to peripheral lymphoid organs, such as spleen and lymph nodes. Both V(D)J recombination and CSR depend on an open chromatin state that makes DNA accessible to specific enzymes, recombination activating gene (RAG), and activation-induced cytidine deaminase (AID). Acetyltransferases GCN5 and PCAF possess redundant functions acetylating histone H3 lysine 9 (H3K9). Here, we generated a mouse model that lacked both GCN5 and PCAF in B cells. Double-deficient mice possessed low levels of mature B cells in the bone marrow and peripheral organs, an accumulation of pro-B cells in bone marrow, and reduced CSR levels. We concluded that both GCN5 and PCAF are required for B-cell development in vivo. MDPI 2021-12-31 /pmc/articles/PMC8773862/ /pubmed/35053209 http://dx.doi.org/10.3390/biom12010061 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Oksenych, Valentyn
Su, Dan
Daniel, Jeremy A.
Acetyltransferases GCN5 and PCAF Are Required for B Lymphocyte Maturation in Mice
title Acetyltransferases GCN5 and PCAF Are Required for B Lymphocyte Maturation in Mice
title_full Acetyltransferases GCN5 and PCAF Are Required for B Lymphocyte Maturation in Mice
title_fullStr Acetyltransferases GCN5 and PCAF Are Required for B Lymphocyte Maturation in Mice
title_full_unstemmed Acetyltransferases GCN5 and PCAF Are Required for B Lymphocyte Maturation in Mice
title_short Acetyltransferases GCN5 and PCAF Are Required for B Lymphocyte Maturation in Mice
title_sort acetyltransferases gcn5 and pcaf are required for b lymphocyte maturation in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773862/
https://www.ncbi.nlm.nih.gov/pubmed/35053209
http://dx.doi.org/10.3390/biom12010061
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