ArticleThe Journal of clinical investigation2010
Mutation of a barrier insulator in the human ankyrin-1 gene is associated with hereditary spherocytosis.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 34 citations in OpenAlex.
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- Asthma-associated genetic variants induce IL33 differential expression through an enhancer-blocking regulatory region.Nature communications · 2021Article
- Genetics and Genomics Approaches for Diagnosis and Research Into Hereditary Anemias.Frontiers in physiology · 2020Review
- Gene Addition Strategies for β-Thalassemia and Sickle Cell Anemia.Advances in experimental medicine and biology · 2017Review
- Insight into GATA1 transcriptional activity through interrogation of cis elements disrupted in human erythroid disorders.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- CTCF and CohesinSA-1 Mark Active Promoters and Boundaries of Repressive Chromatin Domains in Primary Human Erythroid Cells.PloS one · 2016Article
- The human ankyrin 1 promoter insulator sustains gene expression in a β-globin lentiviral vector in hematopoietic stem cells.Molecular therapy. Methods & clinical development · 2015Article
- An insulator element located at the cyclin B1 interacting protein 1 gene locus is highly conserved among mammalian species.PloS one · 2015Article
- A review of therapeutic prospects of non-viral gene therapy in the retinal pigment epithelium.Biomaterials · 2013Review
- Gene therapy for hemoglobinopathies: progress and challenges.Translational research : the journal of laboratory and clinical medicine · 2013Review
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- Chromatin boundaries require functional collaboration between the hSET1 and NURF complexes.Blood · 2011Article
- The use of chromatin insulators to improve the expression and safety of integrating gene transfer vectors.Human gene therapy · 2011Review
- Learning about genomics and disease from the anucleate human red blood cell.The Journal of clinical investigation · 2010Article
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8 authors at 2 institutions in 1 country.
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Abstract
Defects of the ankyrin-1 gene are the most common cause in humans of hereditary spherocytosis, an inherited anemia that affects patients of all ethnic groups. In some kindreds, linked -108/-153 nucleotide substitutions have been found in the upstream region of the ankyrin gene promoter that is active in erythroid cells. In vivo, the ankyrin erythroid promoter and its upstream region direct position-independent, uniform expression, a property of barrier insulators. Using human erythroid cell lines and primary cells and transgenic mice, here we have demonstrated that a region upstream of the erythroid promoter is a barrier insulator in vivo in erythroid cells. The region exhibited both functional and structural characteristics of a barrier, including prevention of gene silencing in an in vivo functional assay, appropriate chromatin configuration, and occupancy by barrier-associated proteins. Fragments with the -108/-153 spherocytosis-associated mutations failed to function as barrier insulators in vivo and demonstrated perturbations in barrier-associated chromatin configuration. In transgenic mice, flanking a mutant -108/-153 ankyrin gene promoter with the well-characterized chicken HS4 barrier insulator restored position-independent, uniform expression at levels comparable to wild-type. These data indicate that an upstream region of the ankyrin-1 erythroid promoter acts as a barrier insulator and identify disruption of the barrier element as a potential pathogenetic mechanism of human disease.
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