Histone methyltransferase DOT1L controls state-specific identity during B cell differentiation.
B-cell differentiation
DOT1L
PRC2
germinal center B cell
plasma cell
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
03 02 2021
03 02 2021
Historique:
received:
26
06
2020
revised:
01
12
2020
accepted:
08
12
2020
pubmed:
8
1
2021
medline:
1
6
2021
entrez:
7
1
2021
Statut:
ppublish
Résumé
Differentiation of naïve peripheral B cells into terminally differentiated plasma cells is characterized by epigenetic alterations, yet the epigenetic mechanisms that control B-cell fate remain unclear. Here, we identified a role for the histone H3K79 methyltransferase DOT1L in controlling B-cell differentiation. Mouse B cells lacking Dot1L failed to establish germinal centers (GC) and normal humoral immune responses in vivo. In vitro, activated B cells in which Dot1L was deleted showed aberrant differentiation and prematurely acquired plasma cell characteristics. Similar results were obtained when DOT1L was chemically inhibited in mature B cells in vitro. Mechanistically, combined epigenomics and transcriptomics analysis revealed that DOT1L promotes expression of a pro-proliferative, pro-GC program. In addition, DOT1L indirectly supports the repression of an anti-proliferative plasma cell differentiation program by maintaining the repression of Polycomb Repressor Complex 2 (PRC2) targets. Our findings show that DOT1L is a key modulator of the core transcriptional and epigenetic landscape in B cells, establishing an epigenetic barrier that warrants B-cell naivety and GC B-cell differentiation.
Identifiants
pubmed: 33410591
doi: 10.15252/embr.202051184
pmc: PMC7857439
doi:
Substances chimiques
Histones
0
Dot1l protein, mouse
EC 2.1.1.-
Methyltransferases
EC 2.1.1.-
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
Banques de données
GEO
['GSE138909', 'GSE138906']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e51184Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
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