GATA-binding factor 1 or GATA-1 (also termed Erythroid transcription factor) is the founding member of the GATA family of transcription factors. This protein is widely expressed throughout vertebrate species. In humans and mice, it is encoded by the GATA1 and Gata1 genes, respectively. These genes are located on the X chromosome in both species.[5][6]
GATA1 regulates the expression (i.e. formation of the genes' products) of an ensemble of genes that mediate the development of red blood cells and platelets. Its critical roles in red blood cell formation include promoting the maturation of precursor cells, e.g. erythroblasts, to red blood cells and stimulating these cells to erect their cytoskeleton and biosynthesize their oxygen-carrying components viz., hemoglobin and heme. GATA1 plays a similarly critical role in the maturation of blood platelets from megakaryoblasts, promegakaryocytes, and megakaryocytes; the latter cells then shed membrane-enclosed fragments of their cytoplasm, i.e. platelets, into the blood.[5][7]
In consequence of the vital role that GATA1 has in the proper maturation of red blood cells and platelets, inactivating mutations in the GATA1 gene (i.e. mutations that result in the production of no, reduced levels of, or a less active GATA1) cause X chromosome-linked anemic and/or bleeding diseases due to the reduced formation and functionality of red blood cells and/or platelets, respectively, or, under certain circumstances, the pathological proliferation of megakaryoblasts. These diseases include transient myeloproliferative disorder occurring in Down syndrome, acute megakaryoblastic leukemia occurring in Down syndrome, Diamond–Blackfan anemia, and various combined anemia-thrombocytopenia syndromes including a gray platelet syndrome-type disorder.[8][9][10]
Reduced levels of GATA1 due to reductions in the translation of GATA1 mRNA into its transcription factor product are associated with promoting the progression of myelofibrosis, i.e. a malignant disease that involves the replacement of bone marrow cells by fibrous tissue and extramedullary hematopoiesis, i.e. the extension of blood cell-forming cells to sites outside of the bone marrow.[11][12]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000102145 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031162 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b Katsumura KR, DeVilbiss AW, Pope NJ, Johnson KD, Bresnick EH (September 2013). "Transcriptional mechanisms underlying hemoglobin synthesis". Cold Spring Harbor Perspectives in Medicine. 3 (9): a015412. doi:10.1101/cshperspect.a015412. PMC 3753722. PMID 23838521.
- ^ Caiulo A, Nicolis S, Bianchi P, Zuffardi O, Bardoni B, Maraschio P, Ottolenghi S, Camerino G, Giglioni B (Feb 1991). "Mapping the gene encoding the human erythroid transcriptional factor NFE1-GF1 to Xp11.23". Human Genetics. 86 (4): 388–90. doi:10.1007/bf00201840. PMID 1999341. S2CID 20747016.
- ^ Gruber TA, Downing JR (August 2015). "The biology of pediatric acute megakaryoblastic leukemia". Blood. 126 (8): 943–9. doi:10.1182/blood-2015-05-567859. PMC 4551356. PMID 26186939.
- ^ Fujiwara T (June 2017). "GATA Transcription Factors: Basic Principles and Related Human Disorders". The Tohoku Journal of Experimental Medicine. 242 (2): 83–91. doi:10.1620/tjem.242.83. PMID 28566565.
- ^ "Entrez Gene: GATA1 GATA binding protein 1 (globin transcription factor 1)".
- ^ Da Costa L, O'Donohue MF, van Dooijeweert B, Albrecht K, Unal S, Ramenghi U, Leblanc T, Dianzani I, Tamary H, Bartels M, Gleizes PE, Wlodarski M, MacInnes AW (October 2017). "Molecular approaches to diagnose Diamond–Blackfan anemia: The EuroDBA experience". European Journal of Medical Genetics. 61 (11): 664–673. doi:10.1016/j.ejmg.2017.10.017. hdl:2318/1676982. PMID 29081386.
- ^ Verrucci M, Pancrazzi A, Aracil M, Martelli F, Guglielmelli P, Zingariello M, Ghinassi B, D'Amore E, Jimeno J, Vannucchi AM, Migliaccio AR (November 2010). "CXCR4-independent rescue of the myeloproliferative defect of the Gata1low myelofibrosis mouse model by Aplidin". Journal of Cellular Physiology. 225 (2): 490–9. doi:10.1002/jcp.22228. PMC 3780594. PMID 20458749.
- ^ Song MK, Park BB, Uhm JE (March 2018). "Understanding Splenomegaly in Myelofibrosis: Association with Molecular Pathogenesis". International Journal of Molecular Sciences. 19 (3): 898. doi:10.3390/ijms19030898. PMC 5877759. PMID 29562644.