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- W1966796613 abstract "Recruitment of somatic hypermutation to the Igκ locus has previously been shown to depend on the enhancer elements, Ei/MAR and E3 ′ . Here we show that these elements are not sufficient to confer mutability. However, hypermutation is effectively targeted to a chimeric β-globin/Igκ transgene whose 5 ′ end is composed of the human β-globin gene (promoter and first two exons) and whose 3 ′ end consists of selected sequences derived from downstream of the Jκ cluster (Ei/MAR, Cκ + flank and E3 ′ ). Thus, multiple downstream Igκ sequences (all derived from 3 ′ of the Jκ cluster) can combine to recruit mutation to a heterologous mutation domain. The location of this hypermutation domain is defined by the position of the transcription start site and this applies even if the Igκ Ei/MAR is positioned upstream of the promoter. Hotspots within the mutation domain are, however, defined by local DNA sequence as evidenced by a new hotspot being created within the β-globin domain by a mutation within the transgene. We propose that multiple, moveable Igκ sequences (that are normally located downstream of the transcription start site) cooperate to bring a hypermutation priming factor to the transcription initiation complex; a mutation domain is thereby created downstream of the promoter but the local sequence defines the detailed pattern of mutation within that domain." @default.
- W1966796613 created "2016-06-24" @default.
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- W1966796613 date "1998-01-01" @default.
- W1966796613 modified "2023-09-26" @default.
- W1966796613 title "Multiple sequences from downstream of the Jκ cluster can combine to recruit somatic hypermutation to a heterologous, upstream mutation domain" @default.
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- W1966796613 doi "https://doi.org/10.1002/(sici)1521-4141(199801)28:01<317::aid-immu317>3.0.co;2-s" @default.
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