OCT2 pre-positioning facilitates cell fate transition and chromatin architecture changes in humoral immunity.
Animals
B-Lymphocytes
/ immunology
Cell Differentiation
/ immunology
Chromatin
/ immunology
Epigenomics
/ methods
Female
Genomics
/ methods
Germinal Center
/ immunology
Immunity, Humoral
/ immunology
Male
Mice
Mice, Inbred C57BL
Organic Cation Transporter 2
/ immunology
Protein Domains
/ immunology
Transcription Factors
/ immunology
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
30
09
2020
accepted:
05
08
2021
pubmed:
25
9
2021
medline:
13
10
2021
entrez:
24
9
2021
Statut:
ppublish
Résumé
During the germinal center (GC) reaction, B cells undergo profound transcriptional, epigenetic and genomic architectural changes. How such changes are established remains unknown. Mapping chromatin accessibility during the humoral immune response, we show that OCT2 was the dominant transcription factor linked to differential accessibility of GC regulatory elements. Silent chromatin regions destined to become GC-specific super-enhancers (SEs) contained pre-positioned OCT2-binding sites in naive B cells (NBs). These preloaded SE 'seeds' featured spatial clustering of regulatory elements enriched in OCT2 DNA-binding motifs that became heavily loaded with OCT2 and its GC-specific coactivator OCAB in GC B cells (GCBs). SEs with high abundance of pre-positioned OCT2 binding preferentially formed long-range chromatin contacts in GCs, to support expression of GC-specifying factors. Gain in accessibility and architectural interactivity of these regions were dependent on recruitment of OCAB. Pre-positioning key regulators at SEs may represent a broadly used strategy for facilitating rapid cell fate transitions.
Identifiants
pubmed: 34556886
doi: 10.1038/s41590-021-01025-w
pii: 10.1038/s41590-021-01025-w
pmc: PMC9829245
mid: NIHMS1848792
doi:
Substances chimiques
Chromatin
0
Organic Cation Transporter 2
0
Slc22a2 protein, mouse
0
Transcription Factors
0
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
1327-1340Subventions
Organisme : NCI NIH HHS
ID : R01 CA178765
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI148387
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA194547
Pays : United States
Organisme : NCI NIH HHS
ID : F31 CA220981
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002384
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA220499
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA229086
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.
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