Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 11 December 2021 / Approved: 14 December 2021 / Online: 14 December 2021 (12:13:03 CET)
Version 2 : Received: 22 December 2021 / Approved: 23 December 2021 / Online: 23 December 2021 (11:29:01 CET)
Version 3 : Received: 28 December 2021 / Approved: 29 December 2021 / Online: 29 December 2021 (12:12:03 CET)

How to cite: Oksenych, V.; Su, D.; Daniel, J.A. Acetyltransferases GCN5 and PCAF are Required for B Lymphocyte Maturation in Mice. Preprints 2021, 2021120231 (doi: 10.20944/preprints202112.0231.v2). Oksenych, V.; Su, D.; Daniel, J.A. Acetyltransferases GCN5 and PCAF are Required for B Lymphocyte Maturation in Mice. Preprints 2021, 2021120231 (doi: 10.20944/preprints202112.0231.v2).

Abstract

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 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 lacks both GCN5 and PCAF in B cells. We found that double-deficient mice possess 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 conclude that both GCN5 and PCAF are required for B cell development in vivo.

Keywords

KAT2A; KAT2B; mice; acetyltransferase; B cell; lymphocyte; class switching

Subject

LIFE SCIENCES, Genetics

Comments (1)

Comment 1
Received: 23 December 2021
Commenter: Valentyn Oksenych
Commenter's Conflict of Interests: Author
Comment: Added coauthors, updated references, corrected English.
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