1992
DOI: 10.1128/mcb.12.4.1561
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Human gamma- to beta-globin gene switching using a mini construct in transgenic mice.

Abstract: The developmental regulation of the human globin genes involves a key switch from fetal (y-) to adult (13-) globin gene expression. It is possible to study the mechanism of this switch by expressing the human globin genes in transgenic mice. Previous work has shown that high-level expression of the human globin genes in transgenic mice requires the presence of the locus control region (LCR) upstream of the genes in the 13-globin locus. High-level, correct developmental regulation of 1-globin gene expression… Show more

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Cited by 65 publications
(67 citation statements)
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“…Expression is seen at both embryonic and adult stages, a finding consistent with loss of stage-specific competition from a linked second gene. Furthermore, appropriate stage-specific expression is observed when the y-and ,B-globin genes are linked in cis and are in their proper orientation with respect to the LCR (9). These experiments support competitive regulation, particularly with respect to silencing of the 13- Proc.…”
supporting
confidence: 51%
See 1 more Smart Citation
“…Expression is seen at both embryonic and adult stages, a finding consistent with loss of stage-specific competition from a linked second gene. Furthermore, appropriate stage-specific expression is observed when the y-and ,B-globin genes are linked in cis and are in their proper orientation with respect to the LCR (9). These experiments support competitive regulation, particularly with respect to silencing of the 13- Proc.…”
supporting
confidence: 51%
“…In transgenic mice, the human 1B-globin gene can be transcribed at all developmental stages, but its expression in embryonic cells is silenced competitively by the upstream sand y-genes (8,9,29). Although down-regulation of the y-gene at the adult stage is initiated in the absence of a linked 13-globin gene (6) (19) or CACC box mutations (18) argues in favor of a cis-acting mechanism for impaired y-silencing.…”
Section: Discussionmentioning
confidence: 99%
“…27 In addition, the sequential looping of the LCR is also responsible for the switch between embryonic, fetal (HbF) and HbA ( Figure 2A). [31][32][33][34] The pattern of expression of the b-globin gene has also been a subject of intense investigations since the switching between HbF and HbA represents an important biological phenomenon and an exemplary model to understand how gene expression is regulated during development. In humans, the switching between the expression of g-globin and b-globin gene occurs in the first three months after birth ( Figure 1B).…”
Section: Globin Synthesis Erythropoiesis and Iron Metabolism: A Compmentioning
confidence: 99%
“…Among the LCR HS sites, HS2 has been found to possess developmental-stageindependent enhancer function (52). It is capable of stimulating the transcription of embryonic ε-, fetal ␥-, and adult ␤-globin genes in erythroid cells at the corresponding developmental stages (9,28,34,42,45,47) and may therefore constitute a major functional component of the LCR. However, a recent targeted deletion study shows that deletion of the HS2 enhancer from the murine LCR generated only mild effects on the expression of the ␤-like globin genes (15), suggesting that HS2 is not essential for LCR function and that LCR function may be due to the contribution of the other HS sites.…”
mentioning
confidence: 99%