NF-κB subunits direct kinetically distinct transcriptional cascades in antigen receptor-activated B cells.
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
07
02
2022
accepted:
15
06
2023
medline:
28
8
2023
pubmed:
1
8
2023
entrez:
31
7
2023
Statut:
ppublish
Résumé
The nuclear factor kappa B (NF-κB) family of transcription factors orchestrates signal-induced gene expression in diverse cell types. Cellular responses to NF-κB activation are regulated at the level of cell and signal specificity, as well as differential use of family members (subunit specificity). Here we used time-dependent multi-omics to investigate the selective functions of Rel and RelA, two closely related NF-κB proteins, in primary B lymphocytes activated via the B cell receptor. Despite large numbers of shared binding sites genome wide, Rel and RelA directed kinetically distinct cascades of gene expression in activated B cells. Single-cell RNA sequencing revealed marked heterogeneity of Rel- and RelA-specific responses, and sequential binding of these factors was not a major mechanism of protracted transcription. Moreover, nuclear co-expression of Rel and RelA led to functional antagonism between the factors. By rigorously identifying the target genes of each NF-κB subunit, these studies provide insights into exclusive functions of Rel and RelA in immunity and cancer.
Identifiants
pubmed: 37524800
doi: 10.1038/s41590-023-01561-7
pii: 10.1038/s41590-023-01561-7
pmc: PMC10457194
doi:
Substances chimiques
NF-kappa B
0
Transcription Factor RelA
0
Receptors, Antigen
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1552-1564Subventions
Organisme : NHGRI NIH HHS
ID : R01 HG009518
Pays : United States
Informations de copyright
© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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