A de novo transcription-dependent TAD boundary underpins critical multiway interactions during antibody class switch recombination.
Mol Cell
; 83(5): 681-697.e7, 2023 03 02.
Article
em En
| MEDLINE
| ID: mdl-36736317
ABSTRACT
Interactions between transcription and cohesin-mediated loop extrusion can influence 3D chromatin architecture. However, their relevance in biology is unclear. Here, we report a direct role for such interactions in the mechanism of antibody class switch recombination (CSR) at the murine immunoglobulin heavy chain locus (Igh). Using Tri-C to measure higher-order multiway interactions on single alleles, we find that the juxtaposition (synapsis) of transcriptionally active donor and acceptor Igh switch (S) sequences, an essential step in CSR, occurs via the interaction of loop extrusion complexes with a de novo topologically associating domain (TAD) boundary formed via transcriptional activity across S regions. Surprisingly, synapsis occurs predominantly in proximity to the 3' CTCF-binding element (3'CBE) rather than the Igh super-enhancer, suggesting a two-step mechanism whereby transcription of S regions is not topologically coupled to synapsis, as has been previously proposed. Altogether, these insights advance our understanding of how 3D chromatin architecture regulates CSR.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Rearranjo Gênico
/
Cadeias Pesadas de Imunoglobulinas
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article