Trial reportHaematologica2014
Identification of a novel erythroid-specific enhancer for the ALAS2 gene and its loss-of-function mutation which is associated with congenital sideroblastic anemia.
Trial report in Haematologica, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 83 citations in OpenAlex.
- A case report of congenital sideroblastic anemia caused by a novel ALAS2 mutation in conjunction with thalassemia.Annals of hematology · 2026Article
- A reversible feedback mechanism regulating mitochondrial heme synthesis.The Journal of biological chemistry · 2026Article
- Article
- Dysregulation of AGO2-miRNA dynamics underlies the AGO2-associated Lessel-Kreienkamp syndrome.Nucleic acids research · 2025Article
- A reversible feedback mechanism regulating mitochondrial heme synthesis.bioRxiv : the preprint server for biology · 2025Article
- Epigenetic Regulation of Erythropoiesis: From Developmental Programs to Therapeutic Targets.International journal of molecular sciences · 2025Review
- An erythroid-specific lentiviral vector improves anemia and iron metabolism in a new model of XLSA.Blood · 2025Article
- Hookworm infection modulates lung and intestinal transcriptomic responses to SARS-CoV-2 in Syrian hamsters.Frontiers in immunology · 2025Article
- Outline of Iron Metabolism, with Emphasis on Erythroid Cells.Mediterranean journal of hematology and infectious diseases · 2025Review
- Endogenous small molecule effectors in GATA transcription factor mechanisms governing biological and pathological processes.Experimental hematology · 2024Review
- Iron Metabolism in the Disorders of Heme Biosynthesis.Metabolites · 2022Review
- Inferring gene regulation from stochastic transcriptional variation across single cells at steady state.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Heme as a differentiation-regulatory transcriptional cofactor.International journal of hematology · 2022Review
- The Use of Next-generation Sequencing in the Diagnosis of Rare Inherited Anaemias: A Joint BSH/EHA Good Practice Paper.HemaSphere · 2022Article
- Congenital sideroblastic anemia model due to ALAS2 mutation is susceptible to ferroptosis.Scientific reports · 2022Article
- Identification of Regulatory Factors and Prognostic Markers in Amyotrophic Lateral Sclerosis.Antioxidants (Basel, Switzerland) · 2022Article
- Case report: An infant boy with X-linked sideroblastic anaemia successfully treated by umbilical cord blood haematopoietic stem cell transplantation.Frontiers in genetics · 2022Article
- Epigenetic and Transcriptional Control of Erythropoiesis.Frontiers in genetics · 2022Review
- [New mutation of congenital sideroblastic anemia: a case report and literature review].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2021Review
- FAM122A Inhibits Erythroid Differentiation through GATA1.Stem cell reports · 2020Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Erythroid-specific 5-aminolevulinate synthase (ALAS2) is the rate-limiting enzyme for heme biosynthesis in erythroid cells, and a missense mutation of the ALAS2 gene is associated with congenital sideroblastic anemia. However, the gene responsible for this form of anemia remains unclear in about 40% of patients. Here, we identify a novel erythroid-specific enhancer of 130 base pairs in the first intron of the ALAS2 gene. The newly identified enhancer contains a cis-acting element that is bound by the erythroid-specific transcription factor GATA1, as confirmed by chromatin immunoprecipitation analysis in vivo and by electrophoretic mobility shift assay in vitro. A promoter activity assay in K562 human erythroleukemia cells revealed that the presence of this 130-base pair region increased the promoter activity of the ALAS2 gene by 10-15-fold. Importantly, two mutations, each of which disrupts the GATA-binding site in the enhancer, were identified in unrelated male patients with congenital sideroblastic anemia, and the lower expression level of ALAS2 mRNA in bone marrow erythroblasts was confirmed in one of these patients. Moreover, GATA1 failed to bind to each mutant sequence at the GATA-binding site, and each mutation abolished the enhancer function on ALAS2 promoter activity in K562 cells. Thus, a mutation at the GATA-binding site in this enhancer may cause congenital sideroblastic anemia. These results suggest that the newly identified intronic enhancer is essential for the expression of the ALAS2 gene in erythroid cells. We propose that the 130-base pair enhancer region located in the first intron of the ALAS2 gene should be examined in patients with congenital sideroblastic anemia in whom the gene responsible is unknown.
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