ArticleMolecular and cellular biology2005
Genome architecture of the human beta-globin locus affects developmental regulation of gene expression.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Co-Regulated Genes and Gene Clusters.Genes · 2021Review
- LCR 5' hypersensitive site specificity for globin gene activation within the active chromatin hub.Nucleic acids research · 2012Article
- Mi2β is required for γ-globin gene silencing: temporal assembly of a GATA-1-FOG-1-Mi2 repressor complex in β-YAC transgenic mice.PLoS genetics · 2012Article
- Induction of Fetal Hemoglobin In Vivo Mediated by a Synthetic γ-Globin Zinc Finger Activator.Anemia · 2012Article
- Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach.Nature genetics · 2011Article
- Article
- Evidence for a bigenic chromatin subdomain in regulation of the fetal-to-adult hemoglobin switch.Molecular and cellular biology · 2009Article
- A T-to-G transversion at nucleotide -567 upstream of HBG2 in a GATA-1 binding motif is associated with elevated hemoglobin F.Molecular and cellular biology · 2008Article
- Silencing of Agamma-globin gene expression during adult definitive erythropoiesis mediated by GATA-1-FOG-1-Mi2 complex binding at the -566 GATA site.Molecular and cellular biology · 2008Article
- Identification of higher-order functional domains in the human ENCODE regions.Genome research · 2007Article
- Phylogenetic comparisons suggest that distance from the locus control region guides developmental expression of primate beta-type globin genes.Proceedings of the National Academy of Sciences of the United States of America · 2006Article
- Persistent fetal gamma-globin expression in adult transgenic mice following deletion of two silencer elements located 3' to the human Agamma-globin gene.Molecular medicine (Cambridge, Mass.)Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
To test the role of gene order in globin gene expression, mutant human beta-globin locus yeast artificial chromosome constructs were used, each having one additional globin gene encoding a "marked" transcript (epsilon(m), gamma(m), or beta(m)) integrated at different locations within the locus. When a beta(m)-globin gene was placed between the locus control region (LCR) and the epsilon-globin gene, beta(m)-globin expression dominated primitive and definitive erythropoiesis; only beta(m)-globin mRNA was detected during the fetal and adult definitive stages of erythropoiesis. When an (A)gamma(m)-globin gene was placed at the same location, (A)gamma(m)-globin was expressed during embryonic erythropoiesis and the fetal liver stage of definitive erythropoiesis but was silenced during the adult stage. The downstream wild-type gamma-globin genes were not expressed. When an epsilon(m)-globin gene was placed between the delta- and beta-globin genes, it remained silent during embryonic erythropoiesis; only the LCR-proximal wild-type epsilon-globin gene was expressed. Placement of a beta(m)-globin gene upstream of the (G)gamma-globin gene resulted in expression of beta(m)-globin in embryonic cells and in a significant decrease in expression of the downstream wild-type beta-globin gene. These results indicate that distance from the LCR, an inherent property of spatial gene order, is a major determinant of temporal gene expression during development.
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