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Gene Review

NFE2  -  nuclear factor, erythroid 2

Homo sapiens

Synonyms: Leucine zipper protein NF-E2, NF-E2, Nuclear factor, erythroid-derived 2 45 kDa subunit, Transcription factor NF-E2 45 kDa subunit, p45, ...


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Disease relevance of NFE2


High impact information on NFE2

  • We also find that NF-E2, another trans-acting factor of the erythrocytic lineage, is present in megakaryocytes [6].
  • We have explored the expression of the transcription factors GATA-1, GATA-2, and NF-E2 in purified early hematopoietic progenitor cells (HPCs) induced to gradual unilineage erythroid or granulocytic differentiation by growth factor stimulus [7].
  • Differential expression and functional role of GATA-2, NF-E2, and GATA-1 in normal adult hematopoiesis [7].
  • One antibody reacts with a mitochondrially located 45 kDa polypeptide (p45) which contains a conserved repetitive amino acid domain. p45 co-purifies with RNA ligase and Tutase in a large ( approximately 700 kDa) RNP, and anti-p45 antibody inhibits in vitro RNA editing [8].
  • To find target genes for p45 NF-E2 in megakaryopoiesis, we used an in vivo immunoselection assay: genomic fragments bound to p45 NF-E2 in the chromatin of a megakaryocytic cell line were immunoprecipitated with an anti-p45 antiserum and cloned [9].

Biological context of NFE2


Anatomical context of NFE2


Associations of NFE2 with chemical compounds


Physical interactions of NFE2


Regulatory relationships of NFE2

  • We previously showed that p45 NF-E2 activated the TXAS promoter in hematopoietic cells via binding to the nucleotides -86/-77 from the transcriptional start site [Yaekashiwa and Wang (2002) J. Biol. Chem. 277, 22497-22508] [26].
  • The abolishment of NF-E2 p45 with NF-E2 antisense oligomers inhibited TPO plus K252a-induced polyploidization [27].
  • These findings place TCF11 as a good candidate for the proposed widely expressed factor(s) known to interact with small Maf proteins and bind NF-E2 sites in a sequence-specific manner resembling NF-E2 [24].
  • Requirement of GATA-1 and p45 NF-E2 expression in butyric acid-induced erythroid differentiation [28].
  • Interleukin-4 downregulates nuclear factor-erythroid 2 (NF-E2) expression in primary megakaryocytes and in megakaryoblastic cell lines [29].

Other interactions of NFE2

  • Analysis of erythroid transcription factor mRNA levels during the time course of BA treatment showed, for the first time, an early and marked (up to three-fold) increase in p45 NF-E2 mRNA, contrasting with that of GATA-1 mRNA (<1.5-fold) [13].
  • Mutation of the NF-E2 site greatly reduced TXAS promoter activity in these two types of cells [26].
  • Two regions homologous to the NFE2 motif are demonstrated to be important for basal expression of human GSS, as mutation of these sites reduced the promoter activity by 66% [23].
  • An analysis of the sauternes mutant, which carries a mutation in the ALAS-2 gene and thus has defective heme synthesis, demonstrates higher levels of NFE2 expression than normal [30].
  • The human homolog of mouse NF-E2 was isolated from the K562 cell line and found to encode a member of the basic leucine-zipper family of DNA-binding regulatory proteins [14].

Analytical, diagnostic and therapeutic context of NFE2


  1. Single-copy transduction and expression of human gamma-globin in K562 erythroleukemia cells using recombinant adeno-associated virus vectors: the effect of mutations in NF-E2 and GATA-1 binding motifs within the hypersensitivity site 2 enhancer. Miller, J.L., Walsh, C.E., Ney, P.A., Samulski, R.J., Nienhuis, A.W. Blood (1993) [Pubmed]
  2. CCAAT enhancer-binding protein alpha suppresses the rat placental glutathione S-transferase gene in normal liver. Ikeda, H., Omoteyama, K., Yoshida, K., Nishi, S., Sakai, M. J. Biol. Chem. (2006) [Pubmed]
  3. Nuclear PLCbeta(1) acts as a negative regulator of p45/NF-E2 expression levels in Friend erythroleukemia cells. Faenza, I., Matteucci, A., Bavelloni, A., Marmiroli, S., Martelli, A.M., Gilmour, R.S., Suh, P.G., Manzoli, L., Cocco, L. Biochim. Biophys. Acta (2002) [Pubmed]
  4. Iron protoporphyrin IX (hemin) but not tin or zinc protoporphyrin IX can stimulate gene expression in K562 cells from enhancer elements containing binding sites for NF-E2. Palma, J.F., Gao, X., Lin, C.H., Wu, S., Solomon, W.B. Blood (1994) [Pubmed]
  5. Altered gene expression in myeloproliferative disorders correlates with activation of signaling by the V617F mutation of Jak2. Kralovics, R., Teo, S.S., Buser, A.S., Brutsche, M., Tiedt, R., Tichelli, A., Passamonti, F., Pietra, D., Cazzola, M., Skoda, R.C. Blood (2005) [Pubmed]
  6. Megakaryocytic and erythrocytic lineages share specific transcription factors. Romeo, P.H., Prandini, M.H., Joulin, V., Mignotte, V., Prenant, M., Vainchenker, W., Marguerie, G., Uzan, G. Nature (1990) [Pubmed]
  7. Differential expression and functional role of GATA-2, NF-E2, and GATA-1 in normal adult hematopoiesis. Labbaye, C., Valtieri, M., Barberi, T., Meccia, E., Masella, B., Pelosi, E., Condorelli, G.L., Testa, U., Peschle, C. J. Clin. Invest. (1995) [Pubmed]
  8. Kinetoplastid RNA-editing-associated protein 1 (REAP-1): a novel editing complex protein with repetitive domains. Madison-Antenucci, S., Sabatini, R.S., Pollard, V.W., Hajduk, S.L. EMBO J. (1998) [Pubmed]
  9. p45 NF-E2 regulates expression of thromboxane synthase in megakaryocytes. Deveaux, S., Cohen-Kaminsky, S., Shivdasani, R.A., Andrews, N.C., Filipe, A., Kuzniak, I., Orkin, S.H., Roméo, P.H., Mignotte, V. EMBO J. (1997) [Pubmed]
  10. hMAF, a small human transcription factor that heterodimerizes specifically with Nrf1 and Nrf2. Marini, M.G., Chan, K., Casula, L., Kan, Y.W., Cao, A., Moi, P. J. Biol. Chem. (1997) [Pubmed]
  11. Chromosomal localization of the human NF-E2 family of bZIP transcription factors by fluorescence in situ hybridization. Chan, J.Y., Cheung, M.C., Moi, P., Chan, K., Kan, Y.W. Hum. Genet. (1995) [Pubmed]
  12. Isolation of a differentially regulated splicing isoform of human NF-E2. Pischedda, C., Cocco, S., Melis, A., Marini, M.G., Kan, Y.W., Cao, A., Moi, P. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  13. Time-course of butyric acid-induced differentiation in human K562 leukemic cell line: rapid increase in gamma-globin, porphobilinogen deaminase and NF-E2 mRNA levels. Chénais, B., Molle, I., Trentesaux, C., Jeannesson, P. Leukemia (1997) [Pubmed]
  14. Isolation of cDNA encoding the human NF-E2 protein. Chan, J.Y., Han, X.L., Kan, Y.W. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  15. Purification of the human NF-E2 complex: cDNA cloning of the hematopoietic cell-specific subunit and evidence for an associated partner. Ney, P.A., Andrews, N.C., Jane, S.M., Safer, B., Purucker, M.E., Weremowicz, S., Morton, C.C., Goff, S.C., Orkin, S.H., Nienhuis, A.W. Mol. Cell. Biol. (1993) [Pubmed]
  16. Interaction of NF-E2 in the human beta-globin locus control region before chromatin remodeling. Onishi, Y., Kiyama, R. J. Biol. Chem. (2003) [Pubmed]
  17. Functional characterization of the two alternative promoters of human p45 NF-E2 gene. Toki, T., Arai, K., Terui, K., Komatsu, N., Yokoyama, M., Katsuoka, F., Yamamoto, M., Ito, E. Exp. Hematol. (2000) [Pubmed]
  18. Sumoylation of p45/NF-E2: nuclear positioning and transcriptional activation of the mammalian beta-like globin gene locus. Shyu, Y.C., Lee, T.L., Ting, C.Y., Wen, S.C., Hsieh, L.J., Li, Y.C., Hwang, J.L., Lin, C.C., Shen, C.K. Mol. Cell. Biol. (2005) [Pubmed]
  19. Increased expression of GATA-1 and NFE-2 erythroid-specific transcription factors during aclacinomycin-mediated differentiation of human erythroleukemic cells. Trentesaux, C., Nyoung, M.N., Aries, A., Morceau, F., Ronchi, A., Ottolenghi, S., Jardillier, J.C., Jeannesson, P. Leukemia (1993) [Pubmed]
  20. Oxygen tension modulates the expression of cytokine receptors, transcription factors, and lineage-specific markers in cultured human megakaryocytes. Mostafa, S.S., Papoutsakis, E.T., Miller, W.M. Exp. Hematol. (2001) [Pubmed]
  21. Inhibitory effect of nitric oxide on chemically induced differentiation of human leukemic K562 cells. Chénais, B., Molle, I., Jeannesson, P. Biochem. Pharmacol. (1999) [Pubmed]
  22. Development of a liquid culture system for megakaryocyte terminal differentiation: fibrinogen promotes megakaryocytopoiesis but not thrombopoiesis. Sato, T., Ono, M., Fujita, H., Tanaka, N., Tomiyama, J., Sakamoto, Y., Takano, Y., Murota, S.I., Morita, I. Br. J. Haematol. (2003) [Pubmed]
  23. Cloning and characterization of the human glutathione synthetase 5'-flanking region. Lee, T.D., Yang, H., Whang, J., Lu, S.C. Biochem. J. (2005) [Pubmed]
  24. Small Maf proteins interact with the human transcription factor TCF11/Nrf1/LCR-F1. Johnsen, O., Skammelsrud, N., Luna, L., Nishizawa, M., Prydz, H., Kolstø, A.B. Nucleic Acids Res. (1996) [Pubmed]
  25. Transcriptional control of the human thromboxane synthase gene in vivo and in vitro. Yaekashiwa, M., Wang, L.H. J. Biol. Chem. (2002) [Pubmed]
  26. Nrf2 regulates thromboxane synthase gene expression in human lung cells. Yaekashiwa, M., Wang, L.H. DNA Cell Biol. (2003) [Pubmed]
  27. Transcription factor NF-E2 is essential for the polyploidization of a human megakaryoblastic cell line, Meg-J. Kobayashi, S., Teramura, M., Ito, K., Iwabe, K., Inaba, T., Mizoguchi, H. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  28. Requirement of GATA-1 and p45 NF-E2 expression in butyric acid-induced erythroid differentiation. Chénais, B. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  29. Interleukin-4 downregulates nuclear factor-erythroid 2 (NF-E2) expression in primary megakaryocytes and in megakaryoblastic cell lines. Catani, L., Amabile, M., Luatti, S., Valdrè, L., Vianelli, N., Martinelli, G., Tura, S. Stem Cells (2001) [Pubmed]
  30. Isolation and characterization of zebrafish NFE2. Pratt, S.J., Drejer, A., Foott, H., Barut, B., Brownlie, A., Postlethwait, J., Kato, Y., Yamamoto, M., Zon, L.I. Physiol. Genomics (2002) [Pubmed]
  31. Characterization of the DNase I hypersensitive site 3' of the human beta globin gene domain. Fleenor, D.E., Kaufman, R.E. Blood (1993) [Pubmed]
  32. Conserved elements containing NF-E2 and tandem GATA binding sites are required for erythroid-specific chromatin structure reorganization within the human beta-globin locus control region. Pomerantz, O., Goodwin, A.J., Joyce, T., Lowrey, C.H. Nucleic Acids Res. (1998) [Pubmed]
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