JH6 downstream intronic sequence is dispensable for RNA polymerase II accumulation and somatic hypermutation of the variable gene in Ramos cells.
Mol Immunol
; 97: 101-108, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29625296
ABSTRACT
Activation-induced deaminase (AID) introduces nucleotide substitutions within the variable region of immunoglobulin genes to promote antibody diversity. This activity, which is limited to 1.5â¯kb downstream of the variable gene promoter, mutates both the coding exon and downstream intronic sequences. We recently reported that RNA polymerase II accumulates in these regions during transcription in mice. This build-up directly correlates with the area that is accessible to AID, and manipulation of RNA polymerase II levels alters the mutation frequency. To address whether the intronic DNA sequence by itself can regulate RNA polymerase II accumulation and promote mutagenesis, we deleted 613â¯bp of DNA downstream of the JH6 intron in the human Ramos B cell line. The loss of this sequence did not alter polymerase abundance or mutagenesis in the variable gene, suggesting that most of the intronic sequence is dispensable for somatic hypermutation.
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MEDLINE
Assunto principal:
RNA Polimerase II
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Região Variável de Imunoglobulina
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Genes de Imunoglobulinas
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Íntrons
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Linfoma de Burkitt
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Hipermutação Somática de Imunoglobulina
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article