GATA1

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GATA binding protein 1 (globin transcription factor 1)
Protein GATA1 PDB 1gnf.png
PDB rendering based on 1gnf.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols GATA1 ; ERYF1; GATA-1; GF-1; GF1; NF-E1; NFE1; XLANP; XLTDA; XLTT
External IDs OMIM305371 MGI95661 HomoloGene1549 GeneCards: GATA1 Gene
RNA expression pattern
PBB GE GATA1 210446 at tn.png
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 HG1436_HG1432_PATCH:
48.65 – 48.65 Mb
Chr X:
7.96 – 7.98 Mb
PubMed search [1] [2]

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]

Function[edit]

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]

Structure[edit]

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.

Disease linkage[edit]

Mutations in GATA1 cause anemias and thrombocytopenia in human patients.[4][5] Disease-causing GATA1 mutations are present in the zinc finger DNA binding domains as well as protein-protein interaction domains of GATA1.[6]

Mutations in exon 2 of the GATA1 gene are present in almost all cases of Down syndrome (DS)-associated acute megakaryoblastic leukemia (AMKL).[7][8] 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.[9] The incidence for the GATA1 mutation in about 4% of Down Syndrome patients, but less than 10% of those with the mutation developed AMKL.[10] 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.[11]

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.[12]

Interactions[edit]

GATA1 has been shown to interact with:

References[edit]

  1. ^ Caiulo A, Nicolis S, Bianchi P, Zuffardi O, Bardoni B, Maraschio P et al. (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. ^ "Entrez Gene: GATA1 GATA binding protein 1 (globin transcription factor 1)". 
  3. ^ 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". The Journal of Biological Chemistry 279 (53): 55024–33. doi:10.1074/jbc.M408886200. PMID 15456760. 
  4. ^ 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. 
  5. ^ Nichols KE, Crispino JD, Poncz M, White JG, Orkin SH, Maris JM et al. (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. 
  6. ^ 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). doi:10.1182/blood-2013-03-488080. PMID 23704091. 
  7. ^ Wechsler J, Greene M, McDevitt MA, Anastasi J, Karp JE, Le Beau MM et al. (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. 
  8. ^ Rainis L, Bercovich D, Strehl S, Teigler-Schlegel A, Stark B, Trka J 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. doi:10.1182/blood-2002-11-3599. PMID 12649131. 
  9. ^ Greene ME, Mundschau G, Wechsler J, McDevitt M, Gamis A, Karp J et al. (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. 
  10. ^ 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. 
  11. ^ 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. 
  12. ^ Kang HJ, Voleti B, Hajszan T, Rajkowska G, Stockmeier CA, Licznerski P et al. (Sep 2012). "Decreased expression of synapse-related genes and loss of synapses in major depressive disorder". Nature Medicine 18 (9). doi:10.1038/nm.2886. PMID 22885997. 
  13. ^ a b Lamonica JM, Deng W, Kadauke S, Campbell AE, Gamsjaeger R, Wang H et al. (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). doi:10.1073/pnas.1102140108. PMID 21536911. 
  14. ^ 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). doi:10.1128/MCB.05413-11. PMID 21555453. 
  15. ^ Stonestrom AJ, Hsu SC, Jahn KS, Huang P, Keller CA, Giardine BM et al. (Feb 2015). "Functions of BET proteins in erythroid gene expression". Blood. doi:10.1182/blood-2014-10-607309. PMID 25696920. 
  16. ^ 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. 
  17. ^ Starck J, Cohet N, Gonnet C, Sarrazin S, Doubeikovskaia Z, Doubeikovski A et al. (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. 
  18. ^ a b c d Watamoto K, Towatari M, Ozawa Y, Miyata Y, Okamoto M, Abe A et al. (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. 
  19. ^ 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. 
  20. ^ Goardon N, Lambert JA, Rodriguez P, Nissaire P, Herblot S, Thibault P et al. (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. 
  21. ^ Labbaye C, Quaranta MT, Pagliuca A, Militi S, Licht JD, Testa U et al. (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. 
  22. ^ 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[edit]

External links[edit]