Erythroid transcription factor also known as GATA-binding factor 1 or GATA-1 is a protein that in humans is encoded by the GATA1gene.[1]
GATA-1 is a member of the GATA transcription factor family and is a key mediator of the development of specific types of blood cells from their precursor cells, termed hematopoietic progenitors or precursors.[2][3] This protein plays a role in erythroid development by regulating a large ensemble of genes that mediate both the development and function of red blood cells. Critical functions in the developing red blood cell (erythroblast) include the establishment of the erythroid cytoskeleton, enzymes that mediate heme biosynthesis, and polypeptide chains that constitute the hemoglobin tetramer. Mutations in the gene encoding GATA-1 have been associated with X-linked dyserythropoietic anemia and thrombocytopenia.[4]
GATA1 is required for the maturation of red blood cells, megakaryocytes, mast cells and eosinophils.[5] GATA1 mutant mice die in early embryonic development due to inability to form mature erythroid cells. GATA1 mutation in humans causes congenital anemias and thrombocytopenias.[6][7]
GATA1 was first described as a red blood cell lineage transcription factor that activates the beta-globin gene.[8] During red blood cell maturation, GATA1 activates nearly all erythroid-specific genes while silencing genes associated with the immature proliferative red blood cell precursor cells (erythroblasts).[9][10] Genome-wide studies have provided evidence that GATA1 activates and represses a large number of genes.[9][10][11][12] Many questions remain unanswered regarding the function of a large number of genes. By contrast, other GATA-1 target genes have established activities to control fundamental cell biological functions, including machinery that controls the ability of erythroid precursor cells to proliferate and proteins that control the capacity of the erythroid precursor cell to remodel its organelles such as mitochondria,[13] proteins that control the RNA content of the erythroid precursor cell,[14] and proteins that control signal transduction networks that orchestrate the many dynamic transitions of the developing erythroid precursor.[15]
Structure
The GATA-1 protein contains multiple functional domains including the C-finger, the N-finger, and N-terminal sequences that have been suggested to constitute a transcriptional activation domain. The C-finger, named for being near the C-terminal, mediates Zinc finger sequence-specific DNA binding. The primary function of the N-finger, named for being near the N-terminal is binding to a cofactor named FOG1 (friend of GATA), although it has also been implicated in binding to naked DNA (DNA studied in the test tube that is not assembled into chromatin). The gene for GATA1 is on the X-chromosome.
Disease linkage
Mutations in GATA1 cause anemias and thrombocytopenia in human patients.[16][17] Disease-causing GATA1 mutations are present in the zinc finger DNA binding domains as well as protein-protein interaction domains of GATA1.[18]
Mutations in exon 2 of the GATA1 gene are present in almost all cases of Down syndrome (DS)-associated acute megakaryoblastic leukemia (AMKL).[19][20] While AMKL is typically associated with the (1;22) translocation and expression of a mutant fusion protein, the genetic alterations that promote individuals with DS-AMKL are related to the GATA1 mutations, and the formation of a truncated transcription factor (GATA1s).
The same mutations in exon 2 of GATA1 present in almost all Down Syndrome-associated transient myeloproliferative disorder (TMD) or transient leukemia (TL), a precursor condition that evolves into AMKL in 30% of patients, that as many as 10% of Down Syndrome children may develop.[21] The incidence for the GATA1 mutation in about 4% of Down Syndrome patients, but less than 10% of those with the mutation developed AMKL.[22] This mutation is present in the fetus, suggesting an early role in leukemogenesis. In addition to screening for TL, a GATA1 mutation at birth might serve as a bio-marker for an increased risk of DS-related AMKL.[23]
Interactions
GATA1 has been shown to interact with several proteins - either directly by binding the protein or indirectly (functional interaction without direct binding).
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2
References
↑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. PMID1999341.
↑Nichols KE, Crispino JD, Poncz M, White JG, Orkin SH, Maris JM, Weiss MJ (Mar 2000). "Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1". Nature Genetics. 24 (3): 266–70. doi:10.1038/73480. PMID10700180.
↑Wechsler J, Greene M, McDevitt MA, Anastasi J, Karp JE, Le Beau MM, Crispino JD (Sep 2002). "Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome". Nature Genetics. 32 (1): 148–52. doi:10.1038/ng955. PMID12172547.
↑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 (Aug 2003). "Mutations in exon 2 of GATA1 are early events in megakaryocytic malignancies associated with trisomy 21". Blood. 102 (3): 981–6. doi:10.1182/blood-2002-11-3599. PMID12649131.
↑Greene ME, Mundschau G, Wechsler J, McDevitt M, Gamis A, Karp J, Gurbuxani S, Arceci R, Crispino JD (2003). "Mutations in GATA1 in both transient myeloproliferative disorder and acute megakaryoblastic leukemia of Down syndrome". Blood Cells, Molecules & Diseases. 31 (3): 351–6. doi:10.1016/j.bcmd.2003.08.001. PMID14636651.
↑Pine SR, Guo Q, Yin C, Jayabose S, Druschel CM, Sandoval C (Sep 2007). "Incidence and clinical implications of GATA1 mutations in newborns with Down syndrome". Blood. 110 (6): 2128–31. doi:10.1182/blood-2007-01-069542. PMID17576817.
↑Shimada A, Xu G, Toki T, Kimura H, Hayashi Y, Ito E (Jan 2004). "Fetal origin of the GATA1 mutation in identical twins with transient myeloproliferative disorder and acute megakaryoblastic leukemia accompanying Down syndrome". Blood. 103 (1): 366. doi:10.1182/blood-2003-09-3219. PMID14684662.
↑Watamoto K, Towatari M, Ozawa Y, Miyata Y, Okamoto M, Abe A, Naoe T, Saito H (Dec 2003). "Altered interaction of HDAC5 with GATA-1 during MEL cell differentiation". Oncogene. 22 (57): 9176–84. doi:10.1038/sj.onc.1206902. PMID14668799.
↑Labbaye C, Quaranta MT, Pagliuca A, Militi S, Licht JD, Testa U, Peschle C (Sep 2002). "PLZF induces megakaryocytic development, activates Tpo receptor expression and interacts with GATA1 protein". Oncogene. 21 (43): 6669–79. doi:10.1038/sj.onc.1205884. PMID12242665.
↑Holmes M, Turner J, Fox A, Chisholm O, Crossley M, Chong B (Aug 1999). "hFOG-2, a novel zinc finger protein, binds the co-repressor mCtBP2 and modulates GATA-mediated activation". The Journal of Biological Chemistry. 274 (33): 23491–8. doi:10.1074/jbc.274.33.23491. PMID10438528.
Further reading
Ohneda K, Yamamoto M (2003). "Roles of hematopoietic transcription factors GATA-1 and GATA-2 in the development of red blood cell lineage". Acta Haematologica. 108 (4): 237–45. doi:10.1159/000065660. PMID12432220.
Gurbuxani S, Vyas P, Crispino JD (Jan 2004). "Recent insights into the mechanisms of myeloid leukemogenesis in Down syndrome". Blood. 103 (2): 399–406. doi:10.1182/blood-2003-05-1556. PMID14512321.
Muntean AG, Ge Y, Taub JW, Crispino JD (Jun 2006). "Transcription factor GATA-1 and Down syndrome leukemogenesis". Leukemia & Lymphoma. 47 (6): 986–97. doi:10.1080/10428190500485810. PMID16840187.
Trainor CD, Evans T, Felsenfeld G, Boguski MS (Jan 1990). "Structure and evolution of a human erythroid transcription factor". Nature. 343 (6253): 92–6. doi:10.1038/343092a0. PMID2104960.
Martin DI, Tsai SF, Orkin SH (Mar 1989). "Increased gamma-globin expression in a nondeletion HPFH mediated by an erythroid-specific DNA-binding factor". Nature. 338 (6214): 435–8. doi:10.1038/338435a0. PMID2467208.
Mouthon MA, Bernard O, Mitjavila MT, Romeo PH, Vainchenker W, Mathieu-Mahul D (Feb 1993). "Expression of tal-1 and GATA-binding proteins during human hematopoiesis". Blood. 81 (3): 647–55. PMID7678994.
Zon LI, Yamaguchi Y, Yee K, Albee EA, Kimura A, Bennett JC, Orkin SH, Ackerman SJ (Jun 1993). "Expression of mRNA for the GATA-binding proteins in human eosinophils and basophils: potential role in gene transcription". Blood. 81 (12): 3234–41. PMID8507862.
Tsang AP, Visvader JE, Turner CA, Fujiwara Y, Yu C, Weiss MJ, Crossley M, Orkin SH (Jul 1997). "FOG, a multitype zinc finger protein, acts as a cofactor for transcription factor GATA-1 in erythroid and megakaryocytic differentiation". Cell. 90 (1): 109–19. doi:10.1016/S0092-8674(00)80318-9. PMID9230307.
Freson K, Devriendt K, Matthijs G, Van Hoof A, De Vos R, Thys C, Minner K, Hoylaerts MF, Vermylen J, Van Geet C (Jul 2001). "Platelet characteristics in patients with X-linked macrothrombocytopenia because of a novel GATA1 mutation". Blood. 98 (1): 85–92. doi:10.1182/blood.V98.1.85. PMID11418466.
Mehaffey MG, Newton AL, Gandhi MJ, Crossley M, Drachman JG (Nov 2001). "X-linked thrombocytopenia caused by a novel mutation of GATA-1". Blood. 98 (9): 2681–8. doi:10.1182/blood.V98.9.2681. PMID11675338.
Crawford SE, Qi C, Misra P, Stellmach V, Rao MS, Engel JD, Zhu Y, Reddy JK (Feb 2002). "Defects of the heart, eye, and megakaryocytes in peroxisome proliferator activator receptor-binding protein (PBP) null embryos implicate GATA family of transcription factors". The Journal of Biological Chemistry. 277 (5): 3585–92. doi:10.1074/jbc.M107995200. PMID11724781.
Freson K, Matthijs G, Thys C, Mariën P, Hoylaerts MF, Vermylen J, Van Geet C (Jan 2002). "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". Human Molecular Genetics. 11 (2): 147–52. doi:10.1093/hmg/11.2.147. PMID11809723.
Molete JM, Petrykowska H, Sigg M, Miller W, Hardison R (Jan 2002). "Functional and binding studies of HS3.2 of the beta-globin locus control region". Gene. 283 (1–2): 185–97. doi:10.1016/S0378-1119(01)00858-7. PMID11867225.
