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; NF-E1; 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 sequence-specific DNA binding • core promoter 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 • sequence-specific DNA binding transcription factor activity • protein binding • zinc ion binding • DNA binding, bending • chromatin DNA binding • sequence-specific DNA binding • C2H2 zinc finger domain binding Cellular component • nucleus • nucleoplasm • transcription factor complex • transcriptional repressor complex Biological process • negative regulation of transcription from RNA polymerase II promoter • 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, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • erythrocyte development • positive regulation of peptidyl-tyrosine phosphorylation • platelet aggregation • transcriptional activation by promoter-enhancer looping • dendritic cell differentiation • cellular response to thyroid hormone stimulus • negative regulation of transcription regulatory region DNA binding • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2623	14460
Ensembl	ENSG00000102145	ENSMUSG00000031162
UniProt	P15976	P17679
RefSeq (mRNA)	NM_002049	NM_008089
RefSeq (protein)	NP_002040	NP_032115
Location (UCSC)	Chr X: 48.79 – 48.79 Mb	Chr X: 7.96 – 7.98 Mb
PubMed search

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 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]

Function

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).

• BRD3^[24][25][26]
• BRD4^[24]
• FLI1^[27][28]
• HDAC1^[29]
• LMO2^[30]
• TAL1^[31]
• ZBTB16^[32]
• ZFPM2^[33]

References

1. 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.
2. Bresnick EH, Katsumura KR, Lee HY, Johnson KD, Perkins AS (2012). "Master regulatory GATA transcription factors: mechanistic principles and emerging links to hematologic malignancies". Nucleic Acids Res. 40 (13): 5819–31. doi:10.1093/nar/gks281. PMC 3401466. PMID 22492510.
3. Bresnick EH, Lee HY, Fujiwara T, Johnson KD, Keles S (2010). "GATA switches as developmental drivers". J. Biol. Chem. 285 (41): 31087–93. doi:10.1074/jbc.R110.159079. PMC 2951181. PMID 20670937.
4. "Entrez Gene: GATA1 GATA binding protein 1 (globin transcription factor 1)".
5. Crispino JD (Feb 2005). "GATA1 in normal and malignant hematopoiesis". Seminars in Cell & Developmental Biology 16 (1): 137–47. doi:10.1016/j.semcdb.2004.11.002. PMID 15659348.
6. Fujiwara Y, Browne CP, Cunniff K, Goff SC, Orkin SH (Oct 1996). "Arrested development of embryonic red cell precursors in mouse embryos lacking transcription factor GATA-1". Proceedings of the National Academy of Sciences of the United States of America 93 (22): 12355–8. doi:10.1073/pnas.93.22.12355. PMC 37995. PMID 8901585.
7. Campbell AE, Wilkinson-White L, Mackay JP, Matthews JM, Blobel GA (Jun 2013). "Analysis of disease-causing GATA1 mutations in murine gene complementation systems". Blood 121 (26): 5218–27. doi:10.1182/blood-2013-03-488080. PMC 3695365. PMID 23704091.
8. Evans T, Reitman M, Felsenfeld G (Aug 1988). "An erythrocyte-specific DNA-binding factor recognizes a regulatory sequence common to all chicken globin genes". Proceedings of the National Academy of Sciences of the United States of America 85 (16): 5976–80. doi:10.1073/pnas.85.16.5976. PMC 281888. PMID 3413070.
9. Welch JJ, Watts JA, Vakoc CR, Yao Y, Wang H, Hardison RC, Blobel GA, Chodosh LA, Weiss MJ (Nov 2004). "Global regulation of erythroid gene expression by transcription factor GATA-1". Blood 104 (10): 3136–47. doi:10.1182/blood-2004-04-1603. PMID 15297311.
10. Cheng Y, Wu W, Kumar SA, Yu D, Deng W, Tripic T, King DC, Chen KB, Zhang Y, Drautz D, Giardine B, Schuster SC, Miller W, Chiaromonte F, Zhang Y, Blobel GA, Weiss MJ, Hardison RC (Dec 2009). "Erythroid GATA1 function revealed by genome-wide analysis of transcription factor occupancy, histone modifications, and mRNA expression". Genome Research 19 (12): 2172–84. doi:10.1101/gr.098921.109. PMC 2792182. PMID 19887574.
11. Yu M, Riva L, Xie H, Schindler Y, Moran TB, Cheng Y, Yu D, Hardison R, Weiss MJ, Orkin SH, Bernstein BE, Fraenkel E, Cantor AB (Nov 2009). "Insights into GATA-1-mediated gene activation versus repression via genome-wide chromatin occupancy analysis". Molecular Cell 36 (4): 682–95. doi:10.1016/j.molcel.2009.11.002. PMC 2800995. PMID 19941827.
12. Fujiwara T, O'Geen H, Keles S, Blahnik K, Linnemann AK, Kang YA, Choi K, Farnham PJ, Bresnick EH (2009). "Discovering hematopoietic mechanisms through genome-wide analysis of GATA factor chromatin occupancy". Mol. Cell 36 (4): 667–81. doi:10.1016/j.molcel.2009.11.001. PMC 2784893. PMID 19941826.
13. Kang YA, Sanalkumar R, O'Geen H, Linnemann AK, Chang CJ, Bouhassira EE, Farnham PJ, Keles S, Bresnick EH (2012). "Autophagy driven by a master regulator of hematopoiesis". Mol. Cell. Biol. 32 (1): 226–39. doi:10.1128/MCB.06166-11. PMC 3255705. PMID 22025678.
14. McIver SC, Kang YA, DeVilbiss AW, O'Driscoll CA, Ouellette JN, Pope NJ, Camprecios G, Chang CJ, Yang D, Bouhassira EE, Ghaffari S, Bresnick EH (2014). "The exosome complex establishes a barricade to erythroid maturation". Blood 124 (14): 2285–97. doi:10.1182/blood-2014-04-571083. PMID 25115889.
15. Hewitt KJ, Kim DH, Devadas P, Prathibha R, Zuo C, Sanalkumar R, Johnson KD, Kang YA, Kim JS, Dewey CN, Keles S, Bresnick EH (2015). "Hematopoietic Signaling Mechanism Revealed from a Stem/Progenitor Cell Cistrome". Mol. Cell 59 (1): 62–74. doi:10.1016/j.molcel.2015.05.020. PMID 26073540.
16. Crispino JD, Weiss MJ (May 2014). "Erythro-megakaryocytic transcription factors associated with hereditary anemia". Blood 123 (20): 3080–8. doi:10.1182/blood-2014-01-453167. PMC 4023417. PMID 24652993.
17. 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. PMID 10700180.
18. Campbell AE, Wilkinson-White L, Mackay JP, Matthews JM, Blobel GA (Jun 2013). "Analysis of disease-causing GATA1 mutations in murine gene complementation systems". Blood 121 (26): 5218–27. doi:10.1182/blood-2013-03-488080. PMC 3695365. PMID 23704091.
19. 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. PMID 12172547.
20. 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. PMID 12649131.
21. 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. PMID 14636651.
22. 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. PMID 17576817.
23. 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. PMID 14684662.
24. Lamonica JM, Deng W, Kadauke S, Campbell AE, Gamsjaeger R, Wang H, Cheng Y, Billin AN, Hardison RC, Mackay JP, Blobel GA (May 2011). "Bromodomain protein Brd3 associates with acetylated GATA1 to promote its chromatin occupancy at erythroid target genes". Proceedings of the National Academy of Sciences of the United States of America 108 (22): E159–68. doi:10.1073/pnas.1102140108. PMC 3107332. PMID 21536911.
25. Gamsjaeger R, Webb SR, Lamonica JM, Billin A, Blobel GA, Mackay JP (Jul 2011). "Structural basis and specificity of acetylated transcription factor GATA1 recognition by BET family bromodomain protein Brd3". Molecular and Cellular Biology 31 (13): 2632–40. doi:10.1128/MCB.05413-11. PMID 21555453.
26. Stonestrom AJ, Hsu SC, Jahn KS, Huang P, Keller CA, Giardine BM, Kadauke S, Campbell AE, Evans P, Hardison RC, Blobel GA (Feb 2015). "Functions of BET proteins in erythroid gene expression". Blood 125: 2825–34. doi:10.1182/blood-2014-10-607309. PMID 25696920.
27. Lahiri K, Dole MG, Vidwans AS, Kamat J, Kandoth P (Apr 1989). "Acute glomerulonephritis". Journal of Tropical Pediatrics 35 (2): 92. doi:10.1093/tropej/35.2.92. PMID 2724402.
28. Starck J, Cohet N, Gonnet C, Sarrazin S, Doubeikovskaia Z, Doubeikovski A, Verger A, Duterque-Coquillaud M, Morle F (Feb 2003). "Functional cross-antagonism between transcription factors FLI-1 and EKLF". Molecular and Cellular Biology 23 (4): 1390–402. doi:10.1128/MCB.23.4.1390-1402.2003. PMC 141137. PMID 12556498.
29. 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. PMID 14668799.
30. Osada H, Grutz G, Axelson H, Forster A, Rabbitts TH (Oct 1995). "Association of erythroid transcription factors: complexes involving the LIM protein RBTN2 and the zinc-finger protein GATA1". Proceedings of the National Academy of Sciences of the United States of America 92 (21): 9585–9. doi:10.1073/pnas.92.21.9585. PMC 40846. PMID 7568177.
31. Goardon N, Lambert JA, Rodriguez P, Nissaire P, Herblot S, Thibault P, Dumenil D, Strouboulis J, Romeo PH, Hoang T (Jan 2006). "ETO2 coordinates cellular proliferation and differentiation during erythropoiesis". The EMBO Journal 25 (2): 357–66. doi:10.1038/sj.emboj.7600934. PMC 1383517. PMID 16407974.
32. 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. PMID 12242665.
33. 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. PMID 10438528.

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. PMID 12432220.
• 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. PMID 14512321.
• 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. PMID 16840187.
• 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. PMID 2104960.
• Zon LI, Tsai SF, Burgess S, Matsudaira P, Bruns GA, Orkin SH (Jan 1990). "The major human erythroid DNA-binding protein (GF-1): primary sequence and localization of the gene to the X chromosome". Proceedings of the National Academy of Sciences of the United States of America 87 (2): 668–72. doi:10.1073/pnas.87.2.668. PMC 53326. PMID 2300555.
• 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. PMID 2467208.
• 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. PMID 7678994.
• 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. PMID 8507862.
• 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. PMID 9230307.
• Rekhtman N, Radparvar F, Evans T, Skoultchi AI (Jun 1999). "Direct interaction of hematopoietic transcription factors PU.1 and GATA-1: functional antagonism in erythroid cells". Genes & Development 13 (11): 1398–411. doi:10.1101/gad.13.11.1398. PMC 316770. PMID 10364157.
• 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. PMID 11418466.
• 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. PMID 11675338.
• 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. PMID 11724781.
• 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. PMID 11809723.
• 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. PMID 11867225.
• Hirasawa R, Shimizu R, Takahashi S, Osawa M, Takayanagi S, Kato Y, Onodera M, Minegishi N, Yamamoto M, Fukao K, Taniguchi H, Nakauchi H, Iwama A (Jun 2002). "Essential and instructive roles of GATA factors in eosinophil development". The Journal of Experimental Medicine 195 (11): 1379–86. doi:10.1084/jem.20020170. PMC 2193540. PMID 12045236.

External links

• Genecards
• GeneReviews/NCBI/NIH/UW entry on GATA1-Related X-Linked Cytopenia
• Geneatlas
• Infobiogen
• Nextbio
• FactorBook GATA1