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GATA1




GATA binding protein 1 (globin transcription factor 1)
PDB rendering based on 1gnf.
Available structures: 1gnf, 1y0j
Identifiers
Symbol(s) GATA1; ERYF1; GF1; NFE1
External IDs OMIM: 305371 MGI: 95661 Homologene: 1549
RNA expression pattern

Additional recommended knowledge

More reference expression data

Orthologs
Human Mouse
Entrez 2623 14460
Ensembl ENSG00000102145 ENSMUSG00000031162
Uniprot P15976 Q3UIH9
Refseq NM_002049 (mRNA)
NP_002040 (protein)
NM_008089 (mRNA)
NP_032115 (protein)
Location Chr X: 48.53 - 48.54 Mb Chr X: 7.12 - 7.12 Mb
Pubmed search [1] [2]

GATA1 is an important transcription factor involved in cell growth and cancer.


This gene encodes a protein which belongs to the GATA family of transcription factors. The protein plays an important role in erythroid development by regulating the switch of fetal hemoglobin to adult hemoglobin. Mutations in this gene have been associated with X-linked dyserythropoietic anemia and thrombocytopenia.[1]


It is essential for erythroid(red blood cell) and megakaryocytic development and mice without GATA1 die as embryos. It helps transcribe the α-spectrin structural protein which is critical for the shape of red blood cells.

The molecule contains three domains the C-finger the N-finger and the Activation Domain. The C-finger, named for being near the C-terminal, has a Zinc finger DNA binding domain. The N-finger, named for being near the N-terminal also binds DNA and a cofactor named FOG-1 (friend of GATA). The Activation Domain is responsible for GATA1's strong transcriptional activation. The gene for GATA1 is on the X-chromosome.

It has been found to enhance the transcription rates by up to 100 times in humans[2].

In 2002, Wechsler J et al[3] demonstrated mutations in exon 2 of the GATA1 gene present in almost all cases of Down syndrome (DS)-associated acute megakaryoblastic leukemia (AMKL).[4]. 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). In 2003, Greene et al showed 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. Pine SR et al demonstrated an incidence for the GATA1 mutation in about 4% of Down Syndrome patients tested, but less than 10% of those with the mutation developed AMKL. Shimada et al. showed in 2004 that the 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.

References

  1. ^ Entrez Gene: GATA1 GATA binding protein 1 (globin transcription factor 1).
  2. ^ Wong EY; Lin J; Forget BG; Bodine DM; Gallagher PG (Dec 2004). "Sequences downstream of the erythroid promoter are required for high level expression of the human alpha-spectrin gene.". J Biol Chem. 279 (53): 55024-33. doi:10.1074/jbc.M408886200. PMID 15456760.
  3. ^ Wechsler J et al (Sep 2002). "Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome". Nat Genet. 32: 148-52. PMID 12172547.
  4. ^ Rainis L et al. (Aug 2003). "Mutations in exon 2 of GATA1 are early events in megakaryocytic malignancies associated with trisomy 21". Blood 102 (3): 981-6. PMID 12649131.

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 Haematol. 108 (4): 237-45. PMID 12432220.
  • Gurbuxani S, Vyas P, Crispino JD (2004). "Recent insights into the mechanisms of myeloid leukemogenesis in Down syndrome.". Blood 103 (2): 399-406. doi:10.1182/blood-2003-05-1556. PMID 14512321.
  • Muntean AG, Ge Y, Taub JW, Crispino JD (2007). "Transcription factor GATA-1 and Down syndrome leukemogenesis.". Leuk. Lymphoma 47 (6): 986-97. doi:10.1080/10428190500485810. PMID 16840187.
  • Caiulo A, Nicolis S, Bianchi P, et al. (1991). "Mapping the gene encoding the human erythroid transcriptional factor NFE1-GF1 to Xp11.23.". Hum. Genet. 86 (4): 388-90. PMID 1999341.
  • Trainor CD, Evans T, Felsenfeld G, Boguski MS (1990). "Structure and evolution of a human erythroid transcription factor.". Nature 343 (6253): 92-6. doi:10.1038/343092a0. PMID 2104960.
  • Zon LI, Tsai SF, Burgess S, et al. (1990). "The major human erythroid DNA-binding protein (GF-1): primary sequence and localization of the gene to the X chromosome.". Proc. Natl. Acad. Sci. U.S.A. 87 (2): 668-72. PMID 2300555.
  • Martin DI, Tsai SF, Orkin SH (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. PMID 2467208.
  • Osada H, Grutz G, Axelson H, et al. (1995). "Association of erythroid transcription factors: complexes involving the LIM protein RBTN2 and the zinc-finger protein GATA1.". Proc. Natl. Acad. Sci. U.S.A. 92 (21): 9585-9. PMID 7568177.
  • Mouthon MA, Bernard O, Mitjavila MT, et al. (1993). "Expression of tal-1 and GATA-binding proteins during human hematopoiesis.". Blood 81 (3): 647-55. PMID 7678994.
  • Zon LI, Yamaguchi Y, Yee K, et al. (1993). "Expression of mRNA for the GATA-binding proteins in human eosinophils and basophils: potential role in gene transcription.". Blood 81 (12): 3234-41. PMID 8507862.
  • Tsang AP, Visvader JE, Turner CA, et al. (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. PMID 9230307.
  • Rekhtman N, Radparvar F, Evans T, Skoultchi AI (1999). "Direct interaction of hematopoietic transcription factors PU.1 and GATA-1: functional antagonism in erythroid cells.". Genes Dev. 13 (11): 1398-411. PMID 10364157.
  • Holmes M, Turner J, Fox A, et al. (1999). "hFOG-2, a novel zinc finger protein, binds the co-repressor mCtBP2 and modulates GATA-mediated activation.". J. Biol. Chem. 274 (33): 23491-8. PMID 10438528.
  • Nichols KE, Crispino JD, Poncz M, et al. (2000). "Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1.". Nat. Genet. 24 (3): 266-70. doi:10.1038/73480. PMID 10700180.
  • Freson K, Devriendt K, Matthijs G, et al. (2001). "Platelet characteristics in patients with X-linked macrothrombocytopenia because of a novel GATA1 mutation.". Blood 98 (1): 85-92. PMID 11418466.
  • Mehaffey MG, Newton AL, Gandhi MJ, et al. (2001). "X-linked thrombocytopenia caused by a novel mutation of GATA-1.". Blood 98 (9): 2681-8. PMID 11675338.
  • Crawford SE, Qi C, Misra P, et al. (2002). "Defects of the heart, eye, and megakaryocytes in peroxisome proliferator activator receptor-binding protein (PBP) null embryos implicate GATA family of transcription factors.". J. Biol. Chem. 277 (5): 3585-92. doi:10.1074/jbc.M107995200. PMID 11724781.
  • Freson K, Matthijs G, Thys C, et al. (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.". Hum. Mol. Genet. 11 (2): 147-52. PMID 11809723.
  • Molete JM, Petrykowska H, Sigg M, et al. (2002). "Functional and binding studies of HS3.2 of the beta-globin locus control region.". Gene 283 (1-2): 185-97. PMID 11867225.
  • Hirasawa R, Shimizu R, Takahashi S, et al. (2002). "Essential and instructive roles of GATA factors in eosinophil development.". J. Exp. Med. 195 (11): 1379-86. PMID 12045236.
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "GATA1". A list of authors is available in Wikipedia.
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