Genomes and Genes
Gene Symbol: GATA-2
Description: GATA binding protein 2
Alias: DCML, IMD21, MONOMAC, NFE1B, endothelial transcription factor GATA-2
- Tsuzuki S, Towatari M, Saito H, Enver T. 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. 2000;20:6276-86 pubmed
- Lee M, Temizer D, Clifford J, Quertermous T. Cloning of the GATA-binding protein that regulates endothelin-1 gene expression in endothelial cells. J Biol Chem. 1991;266:16188-92 pubmed..These data provide the first evidence for a non-erythroid target gene regulated by GATA-2 and indicate that GATA-2 may have a more broad role in transcriptional regulation than the erythroid-specific GATA-1 protein. ..
- Cuellar Rodríguez J, Gea Banacloche J, Freeman A, Hsu A, Zerbe C, Calvo K, et al. Successful allogeneic hematopoietic stem cell transplantation for GATA2 deficiency. Blood. 2011;118:3715-20 pubmed publisher..Nonmyeloablative HSCT in GATA2 deficiency results in reconstitution of the severely deficient monocyte, B-cell, and NK-cell populations and reversal of the clinical phenotype. Registered at www.clinicaltrials.gov as NCT00923364. ..
- Zhang P, Behre G, Pan J, Iwama A, Wara aswapati N, Radomska H, et al. Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1. Proc Natl Acad Sci U S A. 1999;96:8705-10 pubmed..1 protein can inhibit both GATA-1 and GATA-2 transactivation function. Our results suggest that interactions between PU.1 and GATA proteins play a critical role in the decision of stem cells to commit to erythroid vs. myeloid lineages. ..
- Hahn C, Chong C, Carmichael C, Wilkins E, Brautigan P, Li X, et al. Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia. Nat Genet. 2011;43:1012-7 pubmed publisher..Identification of such predisposing genes to familial forms of MDS and AML is critical for more effective diagnosis and prognosis, counseling, selection of related bone marrow transplant donors and development of therapies...
- Greif P, Dufour A, Konstandin N, Ksienzyk B, Zellmeier E, Tizazu B, et al. GATA2 zinc finger 1 mutations associated with biallelic CEBPA mutations define a unique genetic entity of acute myeloid leukemia. Blood. 2012;120:395-403 pubmed publisher..We thus provide evidence for a genetically distinct subgroup of CN-AML. The German AML cooperative group trials 1999 and 2008 are registered with the identifiers NCT00266136 and NCT01382147 at www.clinicaltrials.gov. ..
- Briegel K, Lim K, Plank C, Beug H, Engel J, Zenke M. Ectopic expression of a conditional GATA-2/estrogen receptor chimera arrests erythroid differentiation in a hormone-dependent manner. Genes Dev. 1993;7:1097-109 pubmed..Thus, the GATA-2 transcription factor appears to play a role in regulating the self-renewal capacity of early erythroid progenitor cells. ..
- West R, Hsu A, Holland S, Cuellar Rodríguez J, Hickstein D. Acquired ASXL1 mutations are common in patients with inherited GATA2 mutations and correlate with myeloid transformation. Haematologica. 2014;99:276-81 pubmed publisher..ClinicalTrials.gov identifier NCT00018044, NCT00404560, NCT00001467, NCT00923364.). ..
- Tsai F, Keller G, Kuo F, Weiss M, Chen J, Rosenblatt M, et al. An early haematopoietic defect in mice lacking the transcription factor GATA-2. Nature. 1994;371:221-6 pubmed..We propose that GATA-2 regulates genes controlling growth factor responsiveness or the proliferative capacity of early haematopoietic cells. ..
- Pan X, Minegishi N, Harigae H, Yamagiwa H, Minegishi M, Akine Y, et al. Identification of human GATA-2 gene distal IS exon and its expression in hematopoietic stem cell fractions. J Biochem. 2000;127:105-12 pubmed
- Gudbjartsson D, Bjornsdottir U, Halapi E, Helgadottir A, Sulem P, Jonsdottir G, et al. Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction. Nat Genet. 2009;41:342-7 pubmed publisher..2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls). ..
- Hsu A, Sampaio E, Khan J, Calvo K, Lemieux J, Patel S, et al. Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome. Blood. 2011;118:2653-5 pubmed publisher..Thus, GATA2 joins RUNX1 and CEBPA not only as a familial leukemia gene but also as a cause of a complex congenital immunodeficiency that evolves over decades and combines predisposition to infection and myeloid malignancy. ..
- Wieser R, Volz A, Vinatzer U, Gardiner K, Jager U, Mitterbauer M, et al. Transcription factor GATA-2 gene is located near 3q21 breakpoints in myeloid leukemia. Biochem Biophys Res Commun. 2000;273:239-45 pubmed
- Dasen J, O Connell S, Flynn S, Treier M, Gleiberman A, Szeto D, et al. Reciprocal interactions of Pit1 and GATA2 mediate signaling gradient-induced determination of pituitary cell types. Cell. 1999;97:587-98 pubmed
- Tipping A, Pina C, Castor A, Hong D, Rodrigues N, Lazzari L, et al. High GATA-2 expression inhibits human hematopoietic stem and progenitor cell function by effects on cell cycle. Blood. 2009;113:2661-72 pubmed publisher..Thus, GATA-2 activity inhibits cell cycle in vitro and in vivo, highlighting GATA-2 as a molecular entry point into the transcriptional program regulating quiescence in human hematopoietic stem and progenitor cells. ..
- Pasquet M, BellannÃ© Chantelot C, Tavitian S, Prade N, Beaupain B, LaRochelle O, et al. High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia. Blood. 2013;121:822-9 pubmed publisher..Mutations of key transcription factor in myeloid malignancies. ..
- Johnson K, Hsu A, Ryu M, Wang J, Gao X, Boyer M, et al. Cis-element mutated in GATA2-dependent immunodeficiency governs hematopoiesis and vascular integrity. J Clin Invest. 2012;122:3692-704 pubmed publisher..Thus, the composite element disrupted in a human immunodeficiency is essential for establishment of the murine hematopoietic stem/progenitor cell compartment in the fetal liver and for essential vascular processes. ..
- Nagai T, Harigae H, Ishihara H, Motohashi H, Minegishi N, Tsuchiya S, et al. Transcription factor GATA-2 is expressed in erythroid, early myeloid, and CD34+ human leukemia-derived cell lines. Blood. 1994;84:1074-84 pubmed
- Zhang S, Shi J, Li J. GATA-2 L359 V mutation is exclusively associated with CML progression but not other hematological malignancies and GATA-2 P250A is a novel single nucleotide polymorphism. Leuk Res. 2009;33:1141-3 pubmed publisher..Hence, we concluded GATA-2 L359 V is exclusively associated with CML progression but not other hematological malignancies and P250A is a new single nucleotide polymorphism. ..
- Ostergaard P, Simpson M, Connell F, Steward C, Brice G, Woollard W, et al. Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome). Nat Genet. 2011;43:929-31 pubmed publisher..Our findings indicate that haploinsufficiency of GATA2 underlies primary lymphedema and predisposes to acute myeloid leukemia in this syndrome. ..
- Tsuzuki S, Kitajima K, Nakano T, Glasow A, Zelent A, Enver T. Cross talk between retinoic acid signaling and transcription factor GATA-2. Mol Cell Biol. 2004;24:6824-36 pubmed
- Furuhata A, Murakami M, Ito H, Gao S, Yoshida K, Sobue S, et al. GATA-1 and GATA-2 binding to 3' enhancer of WT1 gene is essential for its transcription in acute leukemia and solid tumor cell lines. Leukemia. 2009;23:1270-7 pubmed publisher..Taken together, these results suggest that GATA-1 and/or GATA-2 binding to a GATA site of the 3' enhancer of WT1 played an important role in WT1 gene expression. ..
- Hsu A, Johnson K, Falcone E, Sanalkumar R, Sanchez L, Hickstein D, et al. GATA2 haploinsufficiency caused by mutations in a conserved intronic element leads to MonoMAC syndrome. Blood. 2013;121:3830-7, S1-7 pubmed publisher..These mutations strongly support the haploinsufficient nature of GATA2 deficiency and identify transcriptional mechanisms and targets that lead to MonoMAC syndrome.
- Zhang R, Min W, Sessa W. 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. 1995;270:15320-6 pubmed..These data demonstrate that the Sp1 site is an important cis-element in the core eNOS promoter. ..
- Grossmann V, Haferlach C, Nadarajah N, Fasan A, Weissmann S, Roller A, et al. CEBPA double-mutated acute myeloid leukaemia harbours concomitant molecular mutations in 76·8% of cases with TET2 and GATA2 alterations impacting prognosis. Br J Haematol. 2013;161:649-58 pubmed publisher..Further, a distinct gene expression profile (GEP) was confirmed for CEBPAdm versus CEBPAsm or CEBPA wild-type cases while no significant changes in GEP were observed related to additional mutations within the CEBPAdm AML. ..
- Kazenwadel J, Secker G, Liu Y, Rosenfeld J, Wildin R, Cuellar Rodríguez J, et al. Loss-of-function germline GATA2 mutations in patients with MDS/AML or MonoMAC syndrome and primary lymphedema reveal a key role for GATA2 in the lymphatic vasculature. Blood. 2012;119:1283-91 pubmed publisher..mutations predispose carriers to familial myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), "MonoMAC" syndrome, and DCML deficiency...
- Luesink M, Hollink I, van der Velden V, Knops R, Boezeman J, de Haas V, et al. High GATA2 expression is a poor prognostic marker in pediatric acute myeloid leukemia. Blood. 2012;120:2064-75 pubmed publisher..We conclude that high GATA2 expression is a novel poor prognostic marker in pediatric AML, which may contribute to better risk-group stratification and risk-adapted therapy in the future. ..
- Gröschel S, Sanders M, Hoogenboezem R, de Wit E, Bouwman B, Erpelinck C, et al. A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia. Cell. 2014;157:369-381 pubmed publisher..confer GATA2 functional haploinsufficiency, previously identified as the cause of sporadic familial AML/MDS and MonoMac/Emberger syndromes...
- Zhang S, Ma L, Huang Q, Li G, Gu B, Gao X, et al. Gain-of-function mutation of GATA-2 in acute myeloid transformation of chronic myeloid leukemia. Proc Natl Acad Sci U S A. 2008;105:2076-81 pubmed publisher..These data strongly suggest that GATA-2 mutations may play a role in acute myeloid transformation in a subset of CML patients. ..
- Dorfman D, Wilson D, Bruns G, Orkin S. Human transcription factor GATA-2. Evidence for regulation of preproendothelin-1 gene expression in endothelial cells. J Biol Chem. 1992;267:1279-85 pubmed..We propose that GATA-2 is the GATA-binding protein required for PPET-1 gene expression in endothelial cells. ..
- Chen Z, An Y, Zhao X. [MonoMAC syndrome]. Zhongguo Dang Dai Er Ke Za Zhi. 2014;16:869-73 pubmedb>MonoMAC syndrome is a newly discovered immune deficiency syndrome caused by GATA-2 mutation, which is an autosomal dominant genetic disease...
- Wen C. Development and characterization of a cell line from tilapia head kidney with melanomacrophage characteristics. Fish Shellfish Immunol. 2016;49:442-9 pubmed publisher..THK cells were subcultured more than 90 times and can be useful for investigating the development and functioning of the teleostean innate immune system. ..
- Guo L, Yamashita H, Kou I, Takimoto A, Meguro Horike M, Horike S, et al. Functional Investigation of a Non-coding Variant Associated with Adolescent Idiopathic Scoliosis in Zebrafish: Elevated Expression of the Ladybird Homeobox Gene Causes Body Axis Deformation. PLoS Genet. 2016;12:e1005802 pubmed publisher..Thus, our study presents a novel pathological feature of LBX1 and its zebrafish homologs in body axis deformation at various stages of embryonic and subsequent growth in zebrafish. ..
- Lizama C, Hawkins J, Schmitt C, Bos F, Zape J, Cautivo K, et al. Repression of arterial genes in hemogenic endothelium is sufficient for haematopoietic fate acquisition. Nat Commun. 2015;6:7739 pubmed publisher..These findings demonstrate that the endothelial haematopoietic fate switch is actively repressed in a population of endothelial cells, and that derepression of these programs augments haematopoietic output. ..
- Yao H, Goldman D, Fan G, Mandel G, Fleming W. The Corepressor Rcor1 Is Essential for Normal Myeloerythroid Lineage Differentiation. Stem Cells. 2015;33:3304-14 pubmed publisher..Taken together, these data demonstrate that Rcor1 is essential for the normal differentiation of myeloerythroid progenitors and for appropriately regulating self-renewal activity in the monocyte lineage. ..
- Kazamel M, Klein C, Benarroch E, Patnaik M, Tracy J. Subacute demyelinating polyradiculoneuropathy complicating Epstein-Barr virus infection in GATA2 haploinsufficiency. Muscle Nerve. 2017;: pubmed publisher..In patients who present in this manner, immunodeficiency syndromes should be considered when lymphomatous infiltration is excluded. Immunotherapy can be helpful. Muscle Nerve, 2017. ..
- Wlodarski M, Collin M, Horwitz M. GATA2 deficiency and related myeloid neoplasms. Semin Hematol. 2017;54:81-86 pubmed publisher..immunodeficiency involving B cells, natural killer cells, CD4+ cells, monocytes and dendritic cells (MonoMAC/DCML), and myeloid neoplasia...
- Shi G, Cui Q, Pan Y, Sheng N, Guo Y, Dai J. 6:2 fluorotelomer carboxylic acid (6:2 FTCA) exposure induces developmental toxicity and inhibits the formation of erythrocytes during zebrafish embryogenesis. Aquat Toxicol. 2017;190:53-61 pubmed publisher..Our results suggest that 6:2 FTCA can cause developmental toxicity in zebrafish embryos, and that FTCAs exhibit greater toxicity than that of PFCAs. ..
- Rastogi N, Abraham R, Chadha R, Thakkar D, Kohli S, Nivargi S, et al. Successful Nonmyeloablative Allogeneic Stem Cell Transplant in a Child With Emberger Syndrome and GATA2 Mutation. J Pediatr Hematol Oncol. 2017;: pubmed publisher..The review of literature showed a total of 28 patients with GATA2 mutation have undergone HSCT mostly nonmyeloablative and overall survival is 75%. Nonmyeloablatove HSCT is feasible and safe for the patients with GATA2 mutation...
- Shobatake R, Takasawa K, Ota H, Itaya Hironaka A, Yamauchi A, Sakuramoto Tsuchida S, et al. Up-regulation of POMC and CART mRNAs by intermittent hypoxia via GATA transcription factors in human neuronal cells. Int J Biochem Cell Biol. 2018;95:100-107 pubmed publisher..IH can have an anorexigenic effect on SAS patients through the transcriptional activation of POMC and CART in the central nervous system. ..
- Goldman O, Cohen I, Gouon Evans V. Functional Blood Progenitor Markers in Developing Human Liver Progenitors. Stem Cell Reports. 2016;7:158-66 pubmed publisher..Knockdown experiments demonstrate that each gene also functions to regulate hepatic fate mostly in a cell-autonomous fashion, revealing unprecedented roles of fetal hematopoietic progenitor markers in human liver progenitors. ..
- Migueles R, Shaw L, Rodrigues N, May G, Henseleit K, Anderson K, et al. Transcriptional regulation of Hhex in hematopoiesis and hematopoietic stem cell ontogeny. Dev Biol. 2017;424:236-245 pubmed publisher..The Hhex ECR thus appears to be a core node for the convergence of the transcription factor network that governs the emergence of HSCs. ..
- Lai T, Li H, Li Y, Hung P, Shyu M, Hu M. Proximal GATA-binding sites are essential for human HSD3B1 gene transcription in the placenta. Sci Rep. 2017;7:4271 pubmed publisher..This study identified GATA motifs as essential control elements for HSD3B1 transcription and GATA2 as a novel transcriptional regulator of HSD3B1 expression in the human placenta. ..
- Vidal S, Rodriguez Bravo V, Quinn S, Rodríguez Barrueco R, Lujambio A, Williams E, et al. A targetable GATA2-IGF2 axis confers aggressiveness in lethal prostate cancer. Cancer Cell. 2015;27:223-39 pubmed publisher..These studies reveal a GATA2-IGF2 aggressiveness axis in lethal prostate cancer and identify a therapeutic opportunity in this challenging disease. ..
- Liau W, Ngoc P, Sanda T. Roles of the RUNX1 Enhancer in Normal Hematopoiesis and Leukemogenesis. Adv Exp Med Biol. 2017;962:139-147 pubmed publisher..In this review, we describe the discovery of eR1 and its roles in normal development and leukemogenesis, as well as its potential applications in stem cell research. ..
- Sotoca A, Prange K, Reijnders B, Mandoli A, Nguyen L, Stunnenberg H, et al. The oncofusion protein FUS-ERG targets key hematopoietic regulators and modulates the all-trans retinoic acid signaling pathway in t(16;21) acute myeloid leukemia. Oncogene. 2016;35:1965-76 pubmed publisher..Together, the results suggest that FUS-ERG acts as a transcriptional repressor of the retinoic acid signaling pathway. ..
- Mazumdar C, Shen Y, Xavy S, Zhao F, Reinisch A, Li R, et al. Leukemia-Associated Cohesin Mutants Dominantly Enforce Stem Cell Programs and Impair Human Hematopoietic Progenitor Differentiation. Cell Stem Cell. 2015;17:675-88 pubmed publisher..Together, these results show that mutant cohesins impair HSPC differentiation by controlling chromatin accessibility and transcription factor activity, possibly contributing to leukemic disease. ..
- Crispino J, Horwitz M. GATA factor mutations in hematologic disease. Blood. 2017;129:2103-2110 pubmed publisher..This review focuses on hematopoietic disorders that are associated with mutations in two prominent GATA family members, GATA1 and GATA2. ..
- Green C, Tawana K, Hills R, Bodor C, Fitzgibbon J, Inglott S, et al. GATA2 mutations in sporadic and familial acute myeloid leukaemia patients with CEBPA mutations. Br J Haematol. 2013;161:701-5 pubmed publisher..CEBPA and GATA2 mutant levels indicated that both mutations were likely to be early events in leukaemogenesis. GATA2 status did not impact on the favourable outcome of CEBPA-double/FLT3-inernal tandem duplication-negative patients. ..
- Xu Y, Li Y, Xu Q, Chen Y, Lv N, Jing Y, et al. Implications of mutational spectrum in myelodysplastic syndromes based on targeted next-generation sequencing. Oncotarget. 2017;8:82475-82490 pubmed publisher..Furthermore, results indicate that MDS could be classified by mutation combinations to guide the administration of individualized therapeutic interventions...
- Ozawa Y, Towatari M, Tsuzuki S, Hayakawa F, Maeda T, Miyata Y, et al. Histone deacetylase 3 associates with and represses the transcription factor GATA-2. Blood. 2001;98:2116-23 pubmed..This is the first demonstration that a tissue-specific transcription factor directly and selectively interacts with HDAC3 and HDAC5 among HDAC family members. ..
- Guan Y, Li W, Hou Z, Han Q, Lan P, Zhang J, et al. HBV suppresses expression of MICA/B on hepatoma cells through up-regulation of transcription factors GATA2 and GATA3 to escape from NK cell surveillance. Oncotarget. 2016;7:56107-56119 pubmed publisher..These findings provide novel mechanisms for the contribution of HBV to hepatoma cells escape from NK cell surveillance. ..
- Bellizzi D, Covello G, Di Cianni F, Tong Q, De Benedictis G. Identification of GATA2 and AP-1 Activator elements within the enhancer VNTR occurring in intron 5 of the human SIRT3 gene. Mol Cells. 2009;28:87-92 pubmed publisher..Therefore, GATA2 and AP-1 are functional sites and the T S> C transition of the second VNTR repeat affects their activity. ..
- Chow P, Rajab N, Chua K, Chan K, Abd Hamid Z. Differential responses of lineages-committed hematopoietic progenitors and altered expression of self-renewal and differentiation-related genes in 1,4-benzoquinone (1,4-BQ) exposure. Toxicol In Vitro. 2018;46:122-128 pubmed publisher..The definite role of lineages specificity and responsive genes in governing the hematotoxicity and leukemogenicity of 1,4-BQ should be further investigated. ..
- Bluteau O, Sebert M, Leblanc T, Peffault De Latour R, Quentin S, Lainey E, et al. A landscape of germline mutations in a cohort of inherited bone marrow failure patients. Blood. 2017;: pubmed publisher..Using a high-throughput sequencing screen to implement precision medicine at diagnosis can improve patient management and family counseling...
- Danis E, Yamauchi T, Echanique K, Haladyna J, Kalkur R, Riedel S, et al. Inactivation of Eed impedes MLL-AF9-mediated leukemogenesis through Cdkn2a-dependent and Cdkn2a-independent mechanisms in a murine model. Exp Hematol. 2015;43:930-935.e6 pubmed publisher..Our data indicate that interference with PRC2 function affects MLL-AF9-mediated leukemogenesis by both Cdkn2a-dependent and Cdkn2a-independent mechanisms. ..
- Spinner M, Sanchez L, Hsu A, Shaw P, Zerbe C, Calvo K, et al. GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity. Blood. 2014;123:809-21 pubmed publisher..001). GATA2 deficiency unites susceptibility to MDS/AML, immunodeficiency, pulmonary disease, and vascular/lymphatic dysfunction. Early genetic diagnosis is critical to direct clinical management, preventive care, and family screening. ..
- Freson K, Thys C, Wittewrongel C, Vermylen J, Hoylaerts M, Van Geet C. Molecular cloning and characterization of the GATA1 cofactor human FOG1 and assessment of its binding to GATA1 proteins carrying D218 substitutions. Hum Genet. 2003;112:42-9 pubmed..The identification of the human FOG1 gene will enable the genetic screening of patients with non X-linked thrombocytopenia and dyserythropoiesis. ..
- Angelos M, Abrahante J, Blum R, Kaufman D. Single Cell Resolution of Human Hematoendothelial Cells Defines Transcriptional Signatures of Hemogenic Endothelium. Stem Cells. 2018;36:206-217 pubmed publisher..Our findings provide a novel strategy to test new genetic targets and optimize the production of definitive hematopoietic cells from human pluripotent stem cells. Stem Cells 2018;36:206-217. ..