GATA2

GATA2
Identifiers
Aliases	GATA2, DCML, IMD21, MONOMAC, NFE1B, GATA binding protein 2
External IDs	MGI: 95662 HomoloGene: 32030 GeneCards: GATA2
Gene ontology Molecular function • RNA polymerase II distal enhancer sequence-specific DNA binding • DNA binding • sequence-specific DNA binding • RNA polymerase II regulatory region sequence-specific DNA binding • RNA polymerase II transcription factor binding • transcription factor activity, sequence-specific DNA binding • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding • zinc ion binding • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • transcription factor binding • chromatin binding • C2H2 zinc finger domain binding • metal ion binding • protein binding • enhancer sequence-specific DNA binding • RNA polymerase II core promoter sequence-specific DNA binding Cellular component • transcription factor complex • nucleoplasm • protein complex • nucleus Biological process • commitment of neuronal cell to specific neuron type in forebrain • positive regulation of phagocytosis • cell differentiation • negative regulation of fat cell differentiation • hemopoiesis • pituitary gland development • positive regulation of phagocytosis, engulfment • regulation of transcription, DNA-templated • positive regulation of erythrocyte differentiation • somatic stem cell population maintenance • negative regulation of macrophage differentiation • GABAergic neuron differentiation • positive regulation of cytosolic calcium ion concentration • negative regulation of fat cell proliferation • negative regulation of neural precursor cell proliferation • embryonic placenta development • neuron migration • blood coagulation • negative regulation of transcription from RNA polymerase II promoter • transcription from RNA polymerase II promoter • cell maturation • semicircular canal development • transcription, DNA-templated • positive regulation of angiogenesis • regulation of primitive erythrocyte differentiation • ventral spinal cord interneuron differentiation • response to lipid • heart development • cell differentiation in hindbrain • central nervous system neuron development • inner ear morphogenesis • positive regulation of neuron differentiation • regulation of histone acetylation • neuron differentiation • regulation of forebrain neuron differentiation • tissue development • phagocytosis • animal organ morphogenesis • urogenital system development • cell fate determination • homeostasis of number of cells within a tissue • definitive hemopoiesis • neuron fate commitment • digestive tract development • negative regulation of myeloid cell differentiation • positive regulation of megakaryocyte differentiation • positive regulation of transcription from RNA polymerase II promoter • negative regulation of Notch signaling pathway • eosinophil fate commitment • positive regulation of mast cell degranulation • cochlea development Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2624	14461
Ensembl	ENSG00000179348	ENSMUSG00000015053
UniProt	P23769	O09100
RefSeq (mRNA)	NM_032638 NM_001145661 NM_001145662	NM_008090
RefSeq (protein)	NP_001139133.1 NP_001139134.1 NP_116027.2	NP_032116.4
Location (UCSC)	Chr 3: 128.48 – 128.49 Mb	Chr 6: 88.19 – 88.21 Mb
PubMed search	[1]	[2]
Wikidata

View/Edit Human

View/Edit Mouse

GATA2 is a human gene which makes a protein called GATA binding protein 2 - a transcription factor.^[3]

Function

The GATA family of transcription factors, which contain zinc fingers in their DNA binding domain, have emerged as candidate regulators of gene expression in hematopoietic cells.^[4] GATA1 is essential for normal primitive and definitive erythropoiesis and is expressed at high levels in erythroid cells, mast cells, and megakaryocytes. GATA2 is expressed in hematopoietic progenitors, including early erythroid cells, mast cells, and megakaryocytes, and also in nonhematopoietic embryonic stem cells. In chicken erythroid progenitors, forced expression of GATA2 promotes proliferation at the expense of differentiation.^[5] GATA2 also plays an essential role in the negative regulation of type 2 deiodinase gene (DIO2).^[6] GATA3 expression is restricted to T-lymphocyte cells and some nonhematopoietic cell types, including embryonic stem cells.^[7]

Interactions

GATA2 has been shown to interact with:

• HDAC3,^[8]
• LMO2,^[9]
• POU1F1,^[10]
• PML^[11]
• SPI1,^[12] and
• ZBTB16.^[13]

Genetic disorders

Multiple mutations on GATA2 gene have been recently implicated as the cause of primary immunodeficiency in patients with MonoMAC Syndrome, and cases of dendritic cell, monocyte, B NK lymphoid deficiency and leukemia.^[14] Mutations in this gene have also been associated with familial myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) and lymphedema, deafness and myelodysplasia (Emberger syndrome).^[15]

Lung cancer

GATA2 has recently been implicated in non-small-cell lung cancer - specifically those tumours that are driven by a faulty Ras protein. Targeting processes that occur downstream of GATA2 signalling with clinically approved drugs had a significant effect in mouse models of the disease.^[16]

See also

• GATA transcription factor
• MonoMAC

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. Lee ME, Temizer DH, Clifford JA, Quertermous T (25 August 1991). "Cloning of the GATA-binding protein that regulates endothelin-1 gene expression in endothelial cells". J. Biol. Chem. 266 (24): 16188–92. PMID 1714909.
4. Tsai FY, Keller G, Kuo FC, Weiss M, Chen J, Rosenblatt M, Alt FW, Orkin SH (September 1994). "An early haematopoietic defect in mice lacking the transcription factor GATA-2". Nature. 371 (6494): 221–6. doi:10.1038/371221a0. PMID 8078582.
5. Briegel K, Lim KC, Plank C, Beug H, Engel JD, Zenke M (June 1993). "Ectopic expression of a conditional GATA-2/estrogen receptor chimera arrests erythroid differentiation in a hormone-dependent manner". Genes Dev. 7 (6): 1097–109. doi:10.1101/gad.7.6.1097. PMID 8504932.
6. Matsunaga, H; Sasaki, S; Suzuki, S; Matsushita, A; Nakamura, H; Nakamura, HM; Hirahara, N; Kuroda, G; Iwaki, H; Ohba, K; Morita, H; Oki, Y; Suda, T (2015). "Essential Role of GATA2 in the Negative Regulation of Type 2 Deiodinase Gene by Liganded Thyroid Hormone Receptor β2 in Thyrotroph.". PLOS ONE. 10 (11): e0142400. doi:10.1371/journal.pone.0142400. PMC 4646574. PMID 26571013.
7. "Entrez Gene: GATA2 GATA binding protein 2".
8. Ozawa Y, Towatari M, Tsuzuki S, Hayakawa F, Maeda T, Miyata Y, Tanimoto M, Saito H (October 2001). "Histone deacetylase 3 associates with and represses the transcription factor GATA-2". Blood. 98 (7): 2116–23. doi:10.1182/blood.v98.7.2116. PMID 11567998.
9. 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.
10. Dasen JS, O'Connell SM, Flynn SE, Treier M, Gleiberman AS, Szeto DP, Hooshmand F, Aggarwal AK, Rosenfeld MG (May 1999). "Reciprocal interactions of Pit1 and GATA2 mediate signaling gradient-induced determination of pituitary cell types". Cell. 97 (5): 587–98. doi:10.1016/s0092-8674(00)80770-9. PMID 10367888.
11. Tsuzuki S, Towatari M, Saito H, Enver T (September 2000). "Potentiation of GATA-2 activity through interactions with the promyelocytic leukemia protein (PML) and the t(15;17)-generated PML-retinoic acid receptor alpha oncoprotein". Mol. Cell. Biol. 20 (17): 6276–86. doi:10.1128/mcb.20.17.6276-6286.2000. PMC 86102. PMID 10938104.
12. Zhang P, Behre G, Pan J, Iwama A, Wara-Aswapati N, Radomska HS, Auron PE, Tenen DG, Sun Z (July 1999). "Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1". Proc. Natl. Acad. Sci. U.S.A. 96 (15): 8705–10. doi:10.1073/pnas.96.15.8705. PMC 17580. PMID 10411939.
13. Tsuzuki S, Enver T (May 2002). "Interactions of GATA-2 with the promyelocytic leukemia zinc finger (PLZF) protein, its homologue FAZF, and the t(11;17)-generated PLZF-retinoic acid receptor alpha oncoprotein". Blood. 99 (9): 3404–10. doi:10.1182/blood.v99.9.3404. PMID 11964310.
14. Dickinson RE, Griffin H, Bigley V, Reynard LN, Hussain R, Haniffa M, Lakey JH, Rahman T, Wang XN, McGovern N, Pagan S, Cookson S, McDonald D, Chua I, Wallis J, Cant A, Wright M, Keavney B, Chinnery PF, Loughlin J, Hambleton S, Santibanez-Koref M, Collin M (September 2011). "Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency". Blood. 118 (10): 2656–8. doi:10.1182/blood-2011-06-360313. PMID 21765025.
15. Lübking A, Vosberg S, Konstandin NP, Dufour A, Graf A, Krebs S, Blum H, Weber A, Lenhoff S, Ehinger M, Spiekermann K, Greif PA, Cammenga J (2015). "Young woman with mild bone marrow dysplasia, GATA2 and ASXL1 mutation treated with allogeneic hematopoietic stem cell transplantation". Leuk Res Rep. 4 (2): 72–5. doi:10.1016/j.lrr.2015.10.001.
16. Kumar MS, Hancock DC, Molina-Arcas M, Steckel M, East P, Diefenbacher M, Armenteros-Monterroso E, Lassailly F, Matthews N, Nye E, Stamp G, Behrens A, Downward J (2012). "The GATA2 Transcriptional Network is Requisite for RAS Oncogene-Driven Non-Small Cell Lung Cancer". Cell. 149 (3): 642–655. doi:10.1016/j.cell.2012.02.059. PMID 22541434.

Further reading

• Minegishi N (2002). "[Transcription factors regulating hematopoiesis: researches spanning from molecule to whole body]". Seikagaku. 74 (5): 398–402. PMID 12073612.
• 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.
• Dorfman DM, Wilson DB, Bruns GA, Orkin SH (1992). "Human transcription factor GATA-2. Evidence for regulation of preproendothelin-1 gene expression in endothelial cells". J. Biol. Chem. 267 (2): 1279–85. PMID 1370462.
• Page RL, Wharton JM, Wilkinson WE, Friedman IM, Claypool WD, Karim A, Kowalski KG, McDonald SJ, Gardiner P, Pritchett EL (1992). "Bidisomide (SC-40230), a new antiarrhythmic agent: initial study of tolerability and pharmacokinetics". Clin. Pharmacol. Ther. 51 (4): 371–8. doi:10.1038/clpt.1992.36. PMID 1563207.
• Lee ME, Temizer DH, Clifford JA, Quertermous T (1991). "Cloning of the GATA-binding protein that regulates endothelin-1 gene expression in endothelial cells". J. Biol. Chem. 266 (24): 16188–92. PMID 1714909.
• Zhang R, Min W, Sessa WC (1995). "Functional analysis of the human endothelial nitric oxide synthase promoter. Sp1 and GATA factors are necessary for basal transcription in endothelial cells". J. Biol. Chem. 270 (25): 15320–6. doi:10.1074/jbc.270.25.15320. PMID 7541039.
• Osada H, Grutz G, Axelson H, Forster A, Rabbitts TH (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.
• Towatari M, May GE, Marais R, Perkins GR, Marshall CJ, Cowley S, Enver T (1995). "Regulation of GATA-2 phosphorylation by mitogen-activated protein kinase and interleukin-3". J. Biol. Chem. 270 (8): 4101–7. doi:10.1074/jbc.270.8.4101. PMID 7876160.
• Tsai FY, Keller G, Kuo FC, Weiss M, Chen J, Rosenblatt M, Alt FW, Orkin SH (1994). "An early haematopoietic defect in mice lacking the transcription factor GATA-2". Nature. 371 (6494): 221–6. doi:10.1038/371221a0. PMID 8078582.
• Briegel K, Lim KC, Plank C, Beug H, Engel JD, Zenke M (1993). "Ectopic expression of a conditional GATA-2/estrogen receptor chimera arrests erythroid differentiation in a hormone-dependent manner". Genes Dev. 7 (6): 1097–109. doi:10.1101/gad.7.6.1097. PMID 8504932.
• Towatari M, Kanei Y, Saito H, Hamaguchi M (1998). "Hematopoietic transcription factor GATA-2 activates transcription from HIV-1 long terminal repeat". AIDS. 12 (3): 253–9. doi:10.1097/00002030-199803000-00002. PMID 9517987.
• Dasen JS, O'Connell SM, Flynn SE, Treier M, Gleiberman AS, Szeto DP, Hooshmand F, Aggarwal AK, Rosenfeld MG (1999). "Reciprocal interactions of Pit1 and GATA2 mediate signaling gradient-induced determination of pituitary cell types". Cell. 97 (5): 587–98. doi:10.1016/S0092-8674(00)80770-9. PMID 10367888.
• Zhang P, Behre G, Pan J, Iwama A, Wara-Aswapati N, Radomska HS, Auron PE, Tenen DG, Sun Z (1999). "Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1". Proc. Natl. Acad. Sci. U.S.A. 96 (15): 8705–10. doi:10.1073/pnas.96.15.8705. PMC 17580. PMID 10411939.
• Wieser R, Volz A, Vinatzer U, Gardiner K, Jäger U, Mitterbauer M, Ziegler A, Fonatsch C (2000). "Transcription factor GATA-2 gene is located near 3q21 breakpoints in myeloid leukemia". Biochem. Biophys. Res. Commun. 273 (1): 239–45. doi:10.1006/bbrc.2000.2947. PMID 10873593.
• Tsuzuki S, Towatari M, Saito H, Enver T (2000). "Potentiation of GATA-2 Activity through Interactions with the Promyelocytic Leukemia Protein (PML) and the t(15;17)-Generated PML-Retinoic Acid Receptor α Oncoprotein". Mol. Cell. Biol. 20 (17): 6276–86. doi:10.1128/MCB.20.17.6276-6286.2000. PMC 86102. PMID 10938104.
• Yamashita K, Discher DJ, Hu J, Bishopric NH, Webster KA (2001). "Molecular regulation of the endothelin-1 gene by hypoxia. Contributions of hypoxia-inducible factor-1, activator protein-1, GATA-2, AND p300/CBP". J. Biol. Chem. 276 (16): 12645–53. doi:10.1074/jbc.M011344200. PMID 11278891.
• Ozawa Y, Towatari M, Tsuzuki S, Hayakawa F, Maeda T, Miyata Y, Tanimoto M, Saito H (2001). "Histone deacetylase 3 associates with and represses the transcription factor GATA-2". Blood. 98 (7): 2116–23. doi:10.1182/blood.V98.7.2116. PMID 11567998.
• Zhang SB, He QY, Zhao H, Gui CY, Jiang C, Qian RL (2002). "Function of GATA transcription factors in hydroxyurea-induced HEL cells". Cell Res. 11 (4): 301–10. doi:10.1038/sj.cr.7290100. PMID 11787775.
• Tsuzuki S, Enver T (2002). "Interactions of GATA-2 with the promyelocytic leukemia zinc finger (PLZF) protein, its homologue FAZF, and the t(11;17)-generated PLZF-retinoic acid receptor alpha oncoprotein". Blood. 99 (9): 3404–10. doi:10.1182/blood.V99.9.3404. PMID 11964310.
• 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 (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.

External links

• GATA2 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook GATA2

This article incorporates text from the United States National Library of Medicine, which is in the public domain.