ArticleBlood cells, molecules & diseases
Deletion of the human beta-globin LCR 5'HS4 or 5'HS1 differentially affects beta-like globin gene expression in beta-YAC transgenic mice.
Article in Blood cells, molecules & diseases. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 13 citations in OpenAlex.
- Creating New β-Globin-Expressing Lentiviral Vectors by High-Resolution Mapping of Locus Control Region Enhancer Sequences.Molecular therapy. Methods & clinical development · 2020Article
- Improved Titer and Gene Transfer by Lentiviral Vectors Using Novel, Small β-Globin Locus Control Region Elements.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- An Optimized Lentiviral Vector Efficiently Corrects the Human Sickle Cell Disease Phenotype.Molecular therapy. Methods & clinical development · 2018Article
- LCR 5' hypersensitive site specificity for globin gene activation within the active chromatin hub.Nucleic acids research · 2012Article
- DNase I hypersensitive site II of the human growth hormone locus control region mediates an essential and distinct long-range enhancer function.The Journal of biological chemistry · 2012Article
- A multiprotein complex necessary for both transcription and DNA replication at the β-globin locus.The EMBO journal · 2010Article
- DNase I hypersensitivity and epsilon-globin transcriptional enhancement are separable in locus control region (LCR) HS1 mutant human beta-globin YAC transgenic mice.The Journal of biological chemistry · 2010Article
- The higher structure of chromatin in the LCR of the beta-globin locus changes during development.Journal of molecular biology · 2009Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
A 213 kb human beta-globin locus yeast artificial chromosome (beta-YAC) was modified by homologous recombination to delete 2.9 kb of cross-species conserved sequence similarity encompassing the LCR 5' hypersensitive site (HS) 4 (Delta5'HS4 beta-YAC). In three transgenic mouse lines, completion of the gamma- to beta-globin switch during definitive erythropoiesis was delayed relative to wild-type beta-YAC mice. In addition, quantitative per-copy human beta-like globin mRNA levels were similar to wild-type beta-YAC transgenic lines, although beta-globin gene expression was slightly decreased in the day 12 fetal liver of Delta5'HS4 beta-YAC mice. A 0.8 kb 5'HS1 fragment was similarly deleted in the YAC. Three Delta5'HS1 beta-YAC transgenic lines were established. epsilon-globin gene expression was markedly reduced, approximately 16 fold, during primitive erythropoiesis compared to wild-type beta-YAC mice, but gamma-globin expression levels were unaffected. However, during the fetal stage of definitive erythropoiesis, gamma-globin gene expression was decreased approximately 4 fold at day 12 and approximately 5 fold at day 14. Temporal developmental expression profiles of the beta-like globin genes were unaffected by deletion of 5'HS1. Decreased expression of the epsilon- and gamma-globin genes is the first phenotype ascribed to a 5'HS1 mutation in the human beta-globin locus, suggesting that this HS does indeed have a role in LCR function beyond simply a combined synergism with the other LCR HSs.
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