Human γ-globin genes silenced independently of other genes in the β-globin locus

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ERYTHROPOIESIS during human development is characterized by switches in expression of β-like globin genes during the transition from the embryonic through fetal to adult stages. Activation and high-level expression of the genes is directed by the locus control region (LCR), located 5′ to the ɛ gene1–3. The location of the LCR and its role in directing high-level expression of the globin genes has led to the suggestion that competition from the β gene for interaction with the LCR has a major role in silencing the fetal γ genes during adult life4,5. We have now constructed lines of transgenic mice containing the human Aγ globin gene linked to the LCR. We observe high-level expression of the transgene in the embryonic stages but silencing of the gene in adult animals. We conclude that the γ gene is not deregulated by the presence of the LCR and that competition from the β gene is not required for silencing of the γ genes in adult life. The silencing is therefore likely to be mediated by stage-specific factors binding to sequences immediately flanking the genes.

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Dillon, N., Grosveld, F. Human γ-globin genes silenced independently of other genes in the β-globin locus. Nature 350, 252–254 (1991) doi:10.1038/350252a0

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