53BP1 Contributes to Igh Locus Chromatin Topology during Class Switch Recombination.
J Immunol
; 198(6): 2434-2444, 2017 03 15.
Article
em En
| MEDLINE
| ID: mdl-28159901
ABSTRACT
In B lymphocytes, Ig class switch recombination (CSR) is induced by activation-induced cytidine deaminase, which initiates a cascade of events leading to DNA double-strand break formation in switch (S) regions. Resolution of DNA double-strand breaks proceeds through formation of S-S synaptic complexes. S-S synapsis is mediated by a chromatin loop that spans the C region domain of the Igh locus. S-S junctions are joined via a nonhomologous end joining DNA repair process. CSR occurs via an intrachromosomal looping out and deletion mechanism that is 53BP1 dependent. However, the mechanism by which 53BP1 facilitates deletional CSR and inhibits inversional switching events remains unknown. We report a novel architectural role for 53BP1 in Igh chromatin looping in mouse B cells. Long-range interactions between the Eµ and 3'Eα enhancers are significantly diminished in the absence of 53BP1. In contrast, germline transcript promoter3'Eα looping interactions are unaffected by 53BP1 deficiency. Furthermore, 53BP1 chromatin occupancy at sites in the Igh locus is B cell specific, is correlated with histone H4 lysine 20 marks, and is subject to chromatin spreading. Thus, 53BP1 is required for three-dimensional organization of the Igh locus and provides a plausible explanation for the link with 53BP1 enforcement of deletional CSR.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
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Cromatina
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Switching de Imunoglobulina
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Isomerases de Ligação Enxofre-Enxofre
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Proteína 1 de Ligação à Proteína Supressora de Tumor p53
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article