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- W2049271350 abstract "Abstract Deletions at the 3′ end of the human β-globin locus are associated with the hereditary persistence of fetal hemoglobin (HPFH) in adults, potentially through the juxtaposition of enhancer elements in the vicinity of the fetal γ-globin genes. We have tested how sequences at the HPFH-2, HPFH-3, and HPFH-6 breakpoints, which act as enhancers in vitro, affect the silencing of a locus control region Aγ (LCRAγ) transgene in the adult stage of mice. We found persistent Aγ expression in the adult blood of most of the multicopy HPFH-2, HPFH-3, or HPFH-6 lines, in contrast to the control LCRAγ lines which were silenced. Cre-mediated generation of single copy lines showed persistent γ gene expression maintained in some of the HPFH-2 and HPFH-6 lines, but not in any of the HPFH-3 or LCRAγ lines. In the HPFH-2 and HPFH-6 lines, persistent γ gene expression correlated with euchromatic transgene integrations. Thus, our observations provide support for a model whereby HPFH conditions arise from the juxtaposition of enhancers as well as permissive chromatin subdomains in the vicinity of the γ-globin genes." @default.
- W2049271350 created "2016-06-24" @default.
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- W2049271350 date "2003-11-01" @default.
- W2049271350 modified "2023-09-27" @default.
- W2049271350 title "Persistent γ-globin expression in adult transgenic mice is mediated by HPFH-2, HPFH-3, and HPFH-6 breakpoint sequences" @default.
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- W2049271350 doi "https://doi.org/10.1182/blood-2003-05-1681" @default.
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