| Written | 2005-02 | Shai Izraeli |
| Pediatric Hemato-Oncology, Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel 52621 |
| Identity |
| Alias_names | erythroid 1 |
| GF1 | |
| Alias_symbol (synonym) | ERYF1 |
| NFE1 | |
| GATA-1 | |
| NF-E1 | |
| Other alias | |
| HGNC (Hugo) | GATA1 |
| LocusID (NCBI) | 2623 |
| Atlas_Id | 40689 |
| Location | Xp11.23 [Link to chromosome band Xp11] |
| Location_base_pair | Starts at 48786574 and ends at 48794310 bp from pter ( according to hg19-Feb_2009) [Mapping GATA1.png] |
| Fusion genes (updated 2016) | HBA1 (16p13.3) / GATA1 (Xp11.23) | MYB (6q23.3) / GATA1 (Xp11.23) |
| DNA/RNA |
| Description | Genomic sequence 7,757 bases, mRNA six exons (five coding) 1497bp. Plus strand |
| Protein |
 | |
| Alternative models for generation of GATA1 isoforms. The full GATA1 protein can only be translated from the full GATA1 mRNA, whereas the GATA1s protein can be translated either from the full gata-1mRNA or from the shorter splice variant in which exon 2 is skipped. | |
| Description | The full length GATA1 protein is 413 amino acids; 42.7 KDa. However two major protein isoforms are formed by alternative splicing of the mRNA and alternative translation initiation sites as shown in the figure. The shorter GATA1 protein (GATA1s) lacks the first 83 aa. ("The N-terminal activation domain AD"). GATA1s is less active in activation of megakaryocytic promoters. Both proteins contain two Zinc finger domains mediating protein interactions and DNA binding. |
| Expression | Bone-Marrow - Erythroid, Megakaryocytic, Mast and Eosonophillic precursors. |
| Localisation | Nuclear |
| Function | Transcription Factor, essential for eryhtroid and megakaryocytic development |
| Homology | A member of the family of GATA proteins. |
| Mutations |
| Germinal | Implicated in germline mutations in the N- Zinc finger domain that mediates the interaction with FOG1 and/or binding to DNA, cause X-linked Dyserythropoietic anemia with thrombocytopenia. The syndrome can be also be manifested only by X-linked macrothrombocytopenia |
| Somatic | see below |
| Implicated in |
| Note | |
| Entity | Acquired somatic mutations in GATA1 occur in virtually all children with Down Syndrome (DS) and congenital transient myeloproliferative syndrome (TMD) or acute megakaryocytic leukemia (AMKL, M7-AML). The mutations have also been detected in umbilical cord blood of DS patients and in fetal liver of aborted DS embryos. The mutations occur in-utero probably during fetal liver hematopoiesis. They consist of insertions, deletions and base substitution in exon 2 and vicinity and all result in elimination of the full length GATA1 protein with preservation of the GATA1s isoform. The presence of GATA1s in the absence of full length GATA1 blocks megakaryocytic differentiation and promote proliferation of megakaryoblasts. The genes on chromosome 21 that promote this abnormality are unknown. GATA1 mutations are almost always associated with the M7 leukemia in DS although they were also described in a pair of twins with acquired trisomy 21 and in one adult non DS patient with M7. The down-regulations of genes regulated by GATA1 may explain the exquisite sensitivity of DS leukemic blasts to ACA-C. |
 | |
| Legend: Example to the distribution of the mutations in children with M7 and DS described in Rainis et al. | |
| Bibliography |
| Natural history of GATA1 mutations in Down syndrome. |
| Ahmed M, Sternberg A, Hall G, Thomas A, Smith O, O'Marcaigh A, Wynn R, Stevens R, Addison M, King D, Stewart B, Gibson B, Roberts I, Vyas P |
| Blood. 2004 ; 103 (7) : 2480-2489. |
| PMID 14656875 |
| Different substitutions at residue D218 of the X-linked transcription factor GATA1 lead to altered clinical severity of macrothrombocytopenia and anemia and are associated with variable skewed X inactivation. |
| Freson K, Matthijs G, Thys C, Mariën P, Hoylaerts MF, Vermylen J, Van Geet C |
| Human molecular genetics. 2002 ; 11 (2) : 147-152. |
| PMID 11809723 |
| The role of cytidine deaminase and GATA1 mutations in the increased cytosine arabinoside sensitivity of Down syndrome myeloblasts and leukemia cell lines. |
| Ge Y, Jensen TL, Stout ML, Flatley RM, Grohar PJ, Ravindranath Y, Matherly LH, Taub JW |
| Cancer research. 2004 ; 64 (2) : 728-735. |
| PMID 14744791 |
| Acquired mutations in GATA1 in neonates with Down's syndrome with transient myeloid disorder. |
| Groet J, McElwaine S, Spinelli M, Rinaldi A, Burtscher I, Mulligan C, Mensah A, Cavani S, Dagna-Bricarelli F, Basso G, Cotter FE, Nizetic D |
| Lancet. 2003 ; 361 (9369) : 1617-1620. |
| PMID 12747884 |
| Recent insights into the mechanisms of myeloid leukemogenesis in Down syndrome. |
| Gurbuxani S, Vyas P, Crispino JD |
| Blood. 2004 ; 103 (2) : 399-406. |
| PMID 14512321 |
| The GATA1 mutation in an adult patient with acute megakaryoblastic leukemia not accompanying Down syndrome. |
| Harigae H, Xu G, Sugawara T, Ishikawa I, Toki T, Ito E |
| Blood. 2004 ; 103 (8) : 3242-3243. |
| PMID 15070711 |
| Origins of leukaemia in children with Down syndrome. |
| Hitzler JK, Zipursky A |
| Nature reviews. Cancer. 2005 ; 5 (1) : 11-20. |
| PMID 15630411 |
| Leukaemia -- a developmental perspective. |
| Izraeli S |
| British journal of haematology. 2004 ; 126 (1) : 3-10. |
| PMID 15198727 |
| A leukemogenic twist for GATA1. |
| Look AT |
| Nature genetics. 2002 ; 32 (1) : 83-84. |
| PMID 12172549 |
| Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1. |
| Nichols KE, Crispino JD, Poncz M, White JG, Orkin SH, Maris JM, Weiss MJ |
| Nature genetics. 2000 ; 24 (3) : 266-270. |
| PMID 10700180 |
| Mutations in exon 2 of GATA1 are early events in megakaryocytic malignancies associated with trisomy 21. |
| Rainis L, Bercovich D, Strehl S, Teigler-Schlegel A, Stark B, Trka J, Amariglio N, Biondi A, Muler I, Rechavi G, Kempski H, Haas OA, Izraeli S |
| Blood. 2003 ; 102 (3) : 981-986. |
| PMID 12649131 |
| Prenatal origin of GATA1 mutations may be an initiating step in the development of megakaryocytic leukemia in Down syndrome. |
| Taub JW, Mundschau G, Ge Y, Poulik JM, Qureshi F, Jensen T, James SJ, Matherly LH, Wechsler J, Crispino JD |
| Blood. 2004 ; 104 (5) : 1588-1589. |
| PMID 15317736 |
| Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome. |
| Wechsler J, Greene M, McDevitt MA, Anastasi J, Karp JE, Le Beau MM, Crispino JD |
| Nature genetics. 2002 ; 32 (1) : 148-152. |
| PMID 12172547 |
| Citation |
| This paper should be referenced as such : |
| Izraeli, S |
| GATA1 (GATA binding protein 1 (globin transcription factor1)) |
| Atlas Genet Cytogenet Oncol Haematol. 2005;9(2):117-118. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Genes/GATA1ID40689chXp11.html |
| Other Leukemias implicated (Data extracted from papers in the Atlas) [ 8 ] |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Fri Jun 30 11:07:32 CEST 2017 |
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