GATA1

GATA binding protein 1 (globin transcription factor 1)
	; PDB rendering based on 1gnf.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1gnf, 1y0j
Identifiers
Symbols	GATA1; ERYF1; GATA-1; GF-1; GF1; NFE1; XLANP; XLTDA; XLTT
External IDs	OMIM: 305371 MGI: 95661 HomoloGene: 1549 GeneCards: GATA1 Gene
Gene Ontology
Molecular function	• transcription regulatory region sequence-specific DNA binding; • RNA polymerase II regulatory region sequence-specific DNA binding; • RNA polymerase II core promoter proximal region sequence-specific DNA binding; • RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription; • RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription; • RNA polymerase II transcription factor binding; • enhancer sequence-specific DNA binding; • p53 binding; • DNA binding; • chromatin binding; • sequence-specific DNA binding transcription factor activity; • protein binding; • zinc ion binding; • DNA binding, bending; • sequence-specific DNA binding; • metal ion binding; • C2H2 zinc finger domain binding;
Cellular component	• nucleus; • nucleoplasm; • transcription factor complex; • nucleolus; • transcriptional repressor complex; • nuclear membrane;
Biological process	• in utero embryonic development; • transcription from RNA polymerase II promoter; • cell-cell signaling; • blood coagulation; • negative regulation of cell proliferation; • male gonad development; • regulation of glycoprotein biosynthetic process; • regulation of definitive erythrocyte differentiation; • erythrocyte differentiation; • megakaryocyte differentiation; • platelet formation; • basophil differentiation; • eosinophil differentiation; • negative regulation of bone mineralization; • positive regulation of osteoblast proliferation; • embryonic hemopoiesis; • eosinophil fate commitment; • negative regulation of apoptotic process; • positive regulation of erythrocyte differentiation; • positive regulation of transcription from RNA polymerase II promoter; • erythrocyte development; • positive regulation of peptidyl-tyrosine phosphorylation; • Sertoli cell development; • platelet aggregation; • cellular response to cAMP; • cellular response to follicle-stimulating hormone stimulus; • transcriptional activation by promoter-enhancer looping; • dendritic cell differentiation; • cellular response to thyroid hormone stimulus; • negative regulation of transcription regulatory region DNA binding;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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Erythroid transcription factor also known as GATA-binding factor 1 or GATA-1 is a protein that in humans is encoded by the GATA1 gene.^[1]

GATA-1 is a member of the GATA transcription factor family and is involved in cell growth and cancer. This protein plays a 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.^[2]

[edit] Function

GATA-1 is essential for erythroid (red blood cell) and megakaryocytic (platelet producing cell) 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.

GATA-1 has been found to enhance the transcription rates of the α-spectrin gene by up to 100 fold in humans.^[3]

[edit] Structure

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 FOG1 (friend of GATA). The Activation Domain is responsible for GATA1's strong transcriptional activation. The gene for GATA1 is on the X-chromosome.

[edit] Disease linkage

Mutations in exon 2 of the GATA1 gene are present in almost all cases of Down syndrome (DS)-associated acute megakaryoblastic leukemia (AMKL).^[4]^[5] 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.^[6] The incidence for the GATA1 mutation in about 4% of Down Syndrome patients, but less than 10% of those with the mutation developed AMKL.^[7] 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.^[8]

Increased levels of GATA1 expression have been found in individuals with major depressive disorder. Expression of GATA1 in the prefrontal cortex results in a decrease of the expression of synapse-related genes, a loss of dendritic spines and dendrites, and can produce depressive behavior in rat models of depression.^[9]

[edit] Interactions

GATA1 has been shown to interact with:

[edit] References

^ Caiulo A, Nicolis S, Bianchi P, Zuffardi O, Bardoni B, Maraschio P, Ottolenghi S, Camerino G, Giglioni B (February 1991). "Mapping the gene encoding the human erythroid transcriptional factor NFE1-GF1 to Xp11.23". Hum. Genet. 86 (4): 388–90. PMID 1999341.
^ "Entrez Gene: GATA1 GATA binding protein 1 (globin transcription factor 1)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2623.
^ Wong EY, Lin J, Forget BG, Bodine DM, Gallagher PG (December 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.
^ Wechsler J, Greene M, McDevitt MA, Anastasi J, Karp JE, Le Beau MM, Crispino JD (September 2002). "Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome". Nat. Genet. 32 (1): 148–52. doi:10.1038/ng955. PMID 12172547.
^ 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 (August 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. PMID 12649131.
^ 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 Mol. Dis. 31 (3): 351–6. doi:10.1016/j.bcmd.2003.08.001. PMID 14636651.
^ Pine SR, Guo Q, Yin C, Jayabose S, Druschel CM, Sandoval C (September 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. PMID 17576817.
^ Shimada A, Xu G, Toki T, Kimura H, Hayashi Y, Ito E (January 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. PMID 14684662.
^ Kang HJ, Voleti B, Hajszan T, Rajkowska G, Stockmeier CA, Licznerski P, Lepack A, Majik MS, Jeong LS, Banasr M, Son H, Duman RS (August 2012). "Decreased expression of synapse-related genes and loss of synapses in major depressive disorder". Nature Medicine 18. doi:10.1038/nm.2886.
^ Lahiri K, Dole MG, Vidwans AS, Kamat J, Kandoth P (April 1989). "Acute glomerulonephritis". J. Trop. Pediatr. 35 (2): 92. PMID 2724402.
^ Starck J, Cohet N, Gonnet C, Sarrazin S, Doubeikovskaia Z, Doubeikovski A, Verger A, Duterque-Coquillaud M, Morle F (February 2003). "Functional cross-antagonism between transcription factors FLI-1 and EKLF". Mol. Cell. Biol. 23 (4): 1390–402. doi:10.1128/MCB.23.4.1390-1402.2003. PMC 141137. PMID 12556498.
^ ^a ^b ^c ^d Watamoto K, Towatari M, Ozawa Y, Miyata Y, Okamoto M, Abe A, Naoe T, Saito H (December 2003). "Altered interaction of HDAC5 with GATA-1 during MEL cell differentiation". Oncogene 22 (57): 9176–84. doi:10.1038/sj.onc.1206902. PMID 14668799.
^ Osada H, Grutz G, Axelson H, Forster A, Rabbitts TH (October 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. doi:10.1073/pnas.92.21.9585. PMC 40846. PMID 7568177.
^ Goardon N, Lambert JA, Rodriguez P, Nissaire P, Herblot S, Thibault P, Dumenil D, Strouboulis J, Romeo PH, Hoang T (January 2006). "ETO2 coordinates cellular proliferation and differentiation during erythropoiesis". EMBO J. 25 (2): 357–66. doi:10.1038/sj.emboj.7600934. PMC 1383517. PMID 16407974.
^ Labbaye C, Quaranta MT, Pagliuca A, Militi S, Licht JD, Testa U, Peschle C (September 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. PMID 12242665.
^ Holmes M, Turner J, Fox A, Chisholm O, Crossley M, Chong B (August 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. doi:10.1074/jbc.274.33.23491. PMID 10438528.

[edit] 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. doi:10.1159/000065660. 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.
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. doi:10.1073/pnas.87.2.668. PMC 53326. 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. doi:10.1073/pnas.92.21.9585. PMC 40846. 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. doi:10.1016/S0092-8674(00)80318-9. 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. doi:10.1101/gad.13.11.1398. PMC 316770. 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. doi:10.1074/jbc.274.33.23491. 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. doi:10.1182/blood.V98.1.85. 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. doi:10.1182/blood.V98.9.2681. 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. doi:10.1093/hmg/11.2.147. 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. doi:10.1016/S0378-1119(01)00858-7. 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. doi:10.1084/jem.20020170. PMC 2193540. PMID 12045236.

[edit] External links

[pmid1999341-1] Caiulo A, Nicolis S, Bianchi P, Zuffardi O, Bardoni B, Maraschio P, Ottolenghi S, Camerino G, Giglioni B (February 1991). "Mapping the gene encoding the human erythroid transcriptional factor NFE1-GF1 to Xp11.23". Hum. Genet. 86 (4): 388–90. PMID 1999341.

[2] "Entrez Gene: GATA1 GATA binding protein 1 (globin transcription factor 1)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2623.

[pmid15456760-3] Wong EY, Lin J, Forget BG, Bodine DM, Gallagher PG (December 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.

[pmid12172547-4] Wechsler J, Greene M, McDevitt MA, Anastasi J, Karp JE, Le Beau MM, Crispino JD (September 2002). "Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome". Nat. Genet. 32 (1): 148–52. doi:10.1038/ng955. PMID 12172547.

[pmid12649131-5] 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 (August 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. PMID 12649131.

[pmid14636651-6] 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 Mol. Dis. 31 (3): 351–6. doi:10.1016/j.bcmd.2003.08.001. PMID 14636651.

[pmid17576817-7] Pine SR, Guo Q, Yin C, Jayabose S, Druschel CM, Sandoval C (September 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. PMID 17576817.

[pmid14684662-8] Shimada A, Xu G, Toki T, Kimura H, Hayashi Y, Ito E (January 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. PMID 14684662.

[9] Kang HJ, Voleti B, Hajszan T, Rajkowska G, Stockmeier CA, Licznerski P, Lepack A, Majik MS, Jeong LS, Banasr M, Son H, Duman RS (August 2012). "Decreased expression of synapse-related genes and loss of synapses in major depressive disorder". Nature Medicine 18. doi:10.1038/nm.2886.

[pmid2724402-10] Lahiri K, Dole MG, Vidwans AS, Kamat J, Kandoth P (April 1989). "Acute glomerulonephritis". J. Trop. Pediatr. 35 (2): 92. PMID 2724402.

[pmid12556498-11] Starck J, Cohet N, Gonnet C, Sarrazin S, Doubeikovskaia Z, Doubeikovski A, Verger A, Duterque-Coquillaud M, Morle F (February 2003). "Functional cross-antagonism between transcription factors FLI-1 and EKLF". Mol. Cell. Biol. 23 (4): 1390–402. doi:10.1128/MCB.23.4.1390-1402.2003. PMC 141137. PMID 12556498.

[pmid14668799-12] Watamoto K, Towatari M, Ozawa Y, Miyata Y, Okamoto M, Abe A, Naoe T, Saito H (December 2003). "Altered interaction of HDAC5 with GATA-1 during MEL cell differentiation". Oncogene 22 (57): 9176–84. doi:10.1038/sj.onc.1206902. PMID 14668799.

[pmid7568177-13] Osada H, Grutz G, Axelson H, Forster A, Rabbitts TH (October 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. doi:10.1073/pnas.92.21.9585. PMC 40846. PMID 7568177.

[pmid16407974-14] Goardon N, Lambert JA, Rodriguez P, Nissaire P, Herblot S, Thibault P, Dumenil D, Strouboulis J, Romeo PH, Hoang T (January 2006). "ETO2 coordinates cellular proliferation and differentiation during erythropoiesis". EMBO J. 25 (2): 357–66. doi:10.1038/sj.emboj.7600934. PMC 1383517. PMID 16407974.

[pmid12242665-15] Labbaye C, Quaranta MT, Pagliuca A, Militi S, Licht JD, Testa U, Peschle C (September 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. PMID 12242665.

[pmid10438528-16] Holmes M, Turner J, Fox A, Chisholm O, Crossley M, Chong B (August 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. doi:10.1074/jbc.274.33.23491. PMID 10438528.

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GATA1

Contents

[edit] Function

[edit] Structure

[edit] Disease linkage

[edit] Interactions

[edit] References

[edit] Further reading

[edit] External links

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