Sequential Enhancer Sequestration Dysregulates Recombination Center Formation at the IgH Locus.
Mol Cell
; 70(1): 21-33.e6, 2018 04 05.
Article
en En
| MEDLINE
| ID: mdl-29576529
ABSTRACT
Immunoglobulin heavy-chain (IgH) genes are assembled by DNA rearrangements that juxtapose a variable (VH), a diversity (DH), and a joining (JH) gene segment. Here, we report that in the absence of intergenic control region 1 (IGCR1), the intronic enhancer (Eµ) associates with the next available CTCF binding site located close to VH81X via putative heterotypic interactions involving YY1 and CTCF. The alternate Eµ/VH81X loop leads to formation of a distorted recombination center and altered DH rearrangements and disrupts chromosome conformation that favors distal VH recombination. Cumulatively, these features drive highly skewed, Eµ-dependent recombination of VH81X. Sequential deletion of CTCF binding regions on IGCR1-deleted alleles suggests that they influence recombination of single proximal VH gene segments. Our observations demonstrate that Eµ interacts differently with IGCR1- or VH-associated CTCF binding sites and thereby identify distinct roles for insulator-like elements in directing enhancer activity.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Recombinación Genética
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Región Variable de Inmunoglobulina
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Elementos de Facilitación Genéticos
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ADN Intergénico
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Ensamble y Desensamble de Cromatina
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Genes de las Cadenas Pesadas de las Inmunoglobulinas
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Células Precursoras de Linfocitos B
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Sitios Genéticos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos