The catalytic domain of the histone methyltransferase NSD2/MMSET is required for the generation of B1 cells in mice.
Animals
Animals, Newborn
B-Lymphocytes
/ metabolism
Catalytic Domain
Germinal Center
/ metabolism
Histone-Lysine N-Methyltransferase
/ chemistry
Histones
/ metabolism
Immunity, Humoral
Immunoglobulin Class Switching
Lysine
/ metabolism
Methylation
Mice, Inbred C57BL
Structure-Activity Relationship
Survival Analysis
B1 cells
MMSET
NSD2
histone methylation
Journal
FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
12
06
2020
revised:
19
07
2020
accepted:
29
07
2020
pubmed:
31
8
2020
medline:
13
5
2021
entrez:
31
8
2020
Statut:
ppublish
Résumé
Humoral immunity in mammals relies on the function of two developmentally and functionally distinct B-cell subsets-B1 and B2 cells. While B2 cells are responsible for the adaptive response to environmental antigens, B1 cells regulate the production of polyreactive and low-affinity antibodies for innate humoral immunity. The molecular mechanism of B-cell specification into different subsets is understudied. In this study, we identified lysine methyltransferase NSD2 (MMSET/WHSC1) as a critical regulator of B1 cell development. In contrast to its minor impact on B2 cells, deletion of the catalytic domain of NSD2 in primary B cells impairs the generation of B1 lineage. Thus, NSD2, a histone H3 K36 dimethylase, is the first-in-class epigenetic regulator of a B-cell lineage in mice.
Identifiants
pubmed: 32862441
doi: 10.1002/1873-3468.13903
pmc: PMC7722058
mid: NIHMS1630050
doi:
Substances chimiques
Histones
0
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
WHSC1 protein, mouse
EC 2.1.1.43
Lysine
K3Z4F929H6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3324-3337Subventions
Organisme : NCI NIH HHS
ID : P01 CA196539
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI118891
Pays : United States
Informations de copyright
© 2020 Federation of European Biochemical Societies.
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