mafg transcription factor


Summary: MafG is a ubiquitously expressed small maf protein that is involved in CELL DIFFERENTIATION of ERYTHROCYTES. It dimerizes with P45 NF-E2 PROTEIN and activates expression of ALPHA-GLOBIN and BETA-GLOBIN.

Top Publications

  1. Motohashi H, Katsuoka F, Miyoshi C, Uchimura Y, Saitoh H, Francastel C, et al. MafG sumoylation is required for active transcriptional repression. Mol Cell Biol. 2006;26:4652-63 pubmed
  2. Yamamoto T, Kyo M, Kamiya T, Tanaka T, Engel J, Motohashi H, et al. Predictive base substitution rules that determine the binding and transcriptional specificity of Maf recognition elements. Genes Cells. 2006;11:575-91 pubmed
    ..This study thus manifests that a clear set of rules pertaining to the cis-acting element determine whether a given MARE preferentially associates with MafG homodimer or with MafG:Nrf2 heterodimer. ..
  3. Katsuoka F, Motohashi H, Ishii T, Aburatani H, Engel J, Yamamoto M. Genetic evidence that small maf proteins are essential for the activation of antioxidant response element-dependent genes. Mol Cell Biol. 2005;25:8044-51 pubmed
    ..These data explicitly demonstrate that small Mafs play critical roles in the inducible expression of a significant portion of ARE-dependent genes. ..
  4. Katsuoka F, Motohashi H, Engel J, Yamamoto M. Nrf2 transcriptionally activates the mafG gene through an antioxidant response element. J Biol Chem. 2005;280:4483-90 pubmed
    ..These results demonstrate that mafG is itself an ARE-dependent gene that is regulated by an Nrf2/small Maf heterodimer and suggest the presence of an autoregulatory feedback pathway for mafG transcriptional regulation. ..
  5. Toki T, Itoh J, Kitazawa J, Arai K, Hatakeyama K, Akasaka J, et al. Human small Maf proteins form heterodimers with CNC family transcription factors and recognize the NF-E2 motif. Oncogene. 1997;14:1901-10 pubmed
    ..The results suggest that the small Maf family proteins function in human cells through interaction with various basic-leucine zipper-type transcription factors. ..
  6. Kurokawa H, Motohashi H, Sueno S, Kimura M, Takagawa H, Kanno Y, et al. Structural basis of alternative DNA recognition by Maf transcription factors. Mol Cell Biol. 2009;29:6232-44 pubmed publisher
    ..This study revealed an alternative DNA recognition mechanism of the bZip factors that bestows specific target gene profiles upon Maf homodimers or Maf-containing heterodimers. ..
  7. Berg D, Gupta A, Richardson M, O Brien L, Calnek D, Grinnell B. Negative regulation of inducible nitric-oxide synthase expression mediated through transforming growth factor-beta-dependent modulation of transcription factor TCF11. J Biol Chem. 2007;282:36837-44 pubmed
    ..Overall, our results demonstrate a novel mechanism by which iNOS expression is regulated in the context of inflammatory activation. ..
  8. Chénais B, Derjuga A, Massrieh W, Red Horse K, Bellingard V, Fisher S, et al. Functional and placental expression analysis of the human NRF3 transcription factor. Mol Endocrinol. 2005;19:125-37 pubmed
    ..Our functional studies suggest that human NRF3 is a potent transcriptional activator. Finally, our expression and induction analyses hint at a possible role of Nrf3 in placental gene expression and development. ..
  9. Ueda K, Xu J, Morimoto H, Kawabe A, Imaoka S. MafG controls the hypoxic response of cells by accumulating HIF-1alpha in the nuclei. FEBS Lett. 2008;582:2357-64 pubmed publisher
    ..The knockdown of MafG did not change total HIF-1alpha protein, but reduced the accumulation of HIF-1alpha in the nuclei. These results suggest that MafG regulates the hypoxic response of cells by detaining HIF-1alpha in the nuclei. ..

More Information


  1. Dhakshinamoorthy S, Jaiswal A. c-Maf negatively regulates ARE-mediated detoxifying enzyme genes expression and anti-oxidant induction. Oncogene. 2002;21:5301-12 pubmed
    ..It reached a plateau at 4 h after t-BHQ treatment. The results together led to the conclusion that c-Maf negatively regulates ARE-mediated detoxifying enzyme genes expression and induction in response to anti-oxidants. ..
  2. Wang X, Chorley B, Pittman G, Kleeberger S, Brothers J, Liu G, et al. Genetic variation and antioxidant response gene expression in the bronchial airway epithelium of smokers at risk for lung cancer. PLoS ONE. 2010;5:e11934 pubmed publisher
    ..These polymorphisms might ultimately contribute to lung cancer risk via their effect on the airway gene expression response to tobacco-smoke exposure. ..
  3. Shimokawa N, Okada J, Miura M. Cloning of MafG homologue from the rat brain by differential display and its expression after hypercapnic stimulation. Mol Cell Biochem. 2000;203:135-41 pubmed
    ..We found that the hypercapnic stimulation induced the gene expression of mafG. These results suggest that MafG may be involved in H+-sensitivity and respiratory regulation in the VMS. ..
  4. Johnsen O, Murphy P, Prydz H, Kolsto A. Interaction of the CNC-bZIP factor TCF11/LCR-F1/Nrf1 with MafG: binding-site selection and regulation of transcription. Nucleic Acids Res. 1998;26:512-20 pubmed
    ..Efficient positive regulation by TCF11 may require alternative partners with perhaps more restricted expression patterns. ..
  5. Ramani K, Tomasi M, Yang H, Ko K, Lu S. Mechanism and significance of changes in glutamate-cysteine ligase expression during hepatic fibrogenesis. J Biol Chem. 2012;287:36341-55 pubmed publisher
    ..In conclusion, sumoylation of Nrf2 and MafG enhances heterodimerization and increases GCLC expression, which keeps HSCs in a quiescent state. Antifibrotic agents require activation of GCLC to fully exert their protective effect. ..
  6. Terui K, Takahashi Y, Kitazawa J, Toki T, Yokoyama M, Ito E. Expression of transcription factors during megakaryocytic differentiation of CD34+ cells from human cord blood induced by thrombopoietin. Tohoku J Exp Med. 2000;192:259-73 pubmed
    ..The dynamic changes in the levels of different transcription factors that occur during primary megakaryocytic differentiation suggest that the levels of these factors may influence the progression to specific hematopoietic pathways. ..
  7. Yamazaki H, Katsuoka F, Motohashi H, Engel J, Yamamoto M. Embryonic lethality and fetal liver apoptosis in mice lacking all three small Maf proteins. Mol Cell Biol. 2012;32:808-16 pubmed publisher
    ..These results thus demonstrate that small Maf proteins are indispensable for embryonic development after E9.5, especially for liver development, but early embryonic development does not require small Mafs. ..
  8. Motohashi H, Shavit J, Igarashi K, Yamamoto M, Engel J. The world according to Maf. Nucleic Acids Res. 1997;25:2953-59 pubmed
  9. Kumaki I, Yang D, Koibuchi N, Takayama K. Neuronal expression of nuclear transcription factor MafG in the rat medulla oblongata after baroreceptor stimulation. Life Sci. 2006;78:1760-6 pubmed
    ..Our results suggest that MafG cooperates with FosB to play critical roles as an immediate early gene in the signal transduction of cardiovascular regulation mediated by baroreceptive signals in the medulla oblongata. ..
  10. Yang H, Ko K, Xia M, Li T, Oh P, Li J, et al. Induction of avian musculoaponeurotic fibrosarcoma proteins by toxic bile acid inhibits expression of glutathione synthetic enzymes and contributes to cholestatic liver injury in mice. Hepatology. 2010;51:1291-301 pubmed publisher
    ..UDCA and SAMe treatment targets this switch. ..
  11. Alam J, Killeen E, Gong P, Naquin R, Hu B, Stewart D, et al. Heme activates the heme oxygenase-1 gene in renal epithelial cells by stabilizing Nrf2. Am J Physiol Renal Physiol. 2003;284:F743-52 pubmed
    ..These results indicate that heme promotes stabilization of Nrf2, leading to accumulation of Nrf2. MafG dimers that bind to StREs to activate the ho-1 gene. ..
  12. Onodera K, Shavit J, Motohashi H, Yamamoto M, Engel J. Perinatal synthetic lethality and hematopoietic defects in compound mafG::mafK mutant mice. EMBO J. 2000;19:1335-45 pubmed
    ..These data provide direct evidence that the small Maf transcription factors play an important regulatory role in erythropoiesis. ..
  13. Kyo M, Yamamoto T, Motohashi H, Kamiya T, Kuroita T, Tanaka T, et al. Evaluation of MafG interaction with Maf recognition element arrays by surface plasmon resonance imaging technique. Genes Cells. 2004;9:153-64 pubmed
    ..These results demonstrate that the double-stranded DNA array fabricated with the modified multistep procedure can be applied for the comprehensive analysis of the transcription factor-DNA interaction. ..
  14. Shimokawa N, Kumaki I, Qiu C, Ohmiya Y, Takayama K, Koibuchi N. Extracellular acidification enhances DNA binding activity of MafG-FosB heterodimer. J Cell Physiol. 2005;205:77-85 pubmed
    ..These results suggest that MafG-FosB complexes are involved in transcriptional regulation in response to extracellular acidification. ..
  15. Li X, Hu Z, Zafar A, Jorgensen M, BUNGERT J, SLAYTON W. Intrinsic and extrinsic effects of mafG deficiency on hematopoietic recovery following bone marrow transplant. Exp Hematol. 2010;38:1251-60 pubmed publisher
    ..Our study demonstrates that mafG expression has intrinsic and extrinsic effects on hematopoietic engraftment following bone marrow transplantation. ..
  16. Kimura M, Yamamoto T, Zhang J, Itoh K, Kyo M, Kamiya T, et al. Molecular basis distinguishing the DNA binding profile of Nrf2-Maf heterodimer from that of Maf homodimer. J Biol Chem. 2007;282:33681-90 pubmed
    ..Our contention is supported that the differential DNA binding specificity between Maf homodimers and Nrf2-Maf heterodimers establishes the differential gene regulation by these dimer-forming transcription factors. ..
  17. Iwata T, Kogame K, Toki T, Yokoyama M, Yamamoto M, Ito E. Structure and chromosome mapping of the human small maf-genes MAFG and MAFK. Cytogenet Cell Genet. 1998;82:88-90 pubmed
    ..Human MAFG and MAFK are located at 17q25 and 7p22, respectively. Thus, small maf genes are not clustered in a single locus. ..
  18. Dhakshinamoorthy S, Jaiswal A. Small maf (MafG and MafK) proteins negatively regulate antioxidant response element-mediated expression and antioxidant induction of the NAD(P)H:Quinone oxidoreductase1 gene. J Biol Chem. 2000;275:40134-41 pubmed
    ..In contrast to Maf-Nrf2, the Maf-Nrf1 heterodimers failed to bind with the NQO1 gene ARE and did not demonstrate the repressive effect in transfection assays. ..
  19. Bloom D, Dhakshinamoorthy S, Jaiswal A. Site-directed mutagenesis of cysteine to serine in the DNA binding region of Nrf2 decreases its capacity to upregulate antioxidant response element-mediated expression and antioxidant induction of NAD(P)H:quinone oxidoreductase1 gene. Oncogene. 2002;21:2191-200 pubmed
    ..Therefore, the C506S mutation in Nrf2 lowered its affinity for the ARE, leading to decreased expression, and antioxidant induction, of NQO1. ..
  20. Kusunoki H, Motohashi H, Katsuoka F, Morohashi A, Yamamoto M, Tanaka T. Solution structure of the DNA-binding domain of MafG. Nat Struct Biol. 2002;9:252-6 pubmed
    ..The structural similarity between MafG and Skn-1 enables us to propose a possible mechanism by which Maf family proteins recognize their consensus DNA sequences. ..
  21. Otsuki A, Suzuki M, Katsuoka F, Tsuchida K, Suda H, Morita M, et al. Unique cistrome defined as CsMBE is strictly required for Nrf2-sMaf heterodimer function in cytoprotection. Free Radic Biol Med. 2016;91:45-57 pubmed publisher
    ..These results demonstrate that the unique cistrome defined as CsMBE is strictly required for the Nrf2-sMaf heterodimer function in cytoprotection and that the roles played by CsMBE differ sharply from those of MARE. ..
  22. Blank V, Kim M, Andrews N. Human MafG is a functional partner for p45 NF-E2 in activating globin gene expression. Blood. 1997;89:3925-35 pubmed
    ..These results indicate that human MafG can serve as a functional partner for p45 NF-E2, and suggest that the p45/MafG heterodimer plays a role in the regulation of erythropoiesis. ..
  23. Katsuoka F, Motohashi H, Tamagawa Y, Kure S, Igarashi K, Engel J, et al. Small Maf compound mutants display central nervous system neuronal degeneration, aberrant transcription, and Bach protein mislocalization coincident with myoclonus and abnormal startle response. Mol Cell Biol. 2003;23:1163-74 pubmed
    ..Thus compound mafG::mafK mutants develop age- and maf gene dosage-dependent cell-autonomous neuronal deficiencies that lead to profound neurological defects. ..
  24. Murphy P, Kolstø A. Expression of the bZIP transcription factor TCF11 and its potential dimerization partners during development. Mech Dev. 2000;97:141-8 pubmed
    ..ATF4 shows evidence of complex regulation during development and shows elevated expression in many of the same sites as TCF11. ..
  25. Shavit J, Motohashi H, Onodera K, Akasaka J, Yamamoto M, Engel J. Impaired megakaryopoiesis and behavioral defects in mafG-null mutant mice. Genes Dev. 1998;12:2164-74 pubmed
    ..These results provide direct evidence that the small Maf transcription factors are vital participants in embryonic development and cellular differentiation. ..
  26. Blank V, Knoll J, Andrews N. Molecular characterization and localization of the human MAFG gene. Genomics. 1997;44:147-9 pubmed
    ..We have mapped the MAFG gene to human chromosome region 17q25 by fluorescence in situ hybridization. Several putative human disease loci have been mapped to this telomeric portion of chromosome 17. ..
  27. Motohashi H. [Small Maf proteins as transcription factors regulating maturation and maintenance of the cell]. Seikagaku. 2003;75:1193-201 pubmed
  28. Catani L, Vianelli N, Amabile M, Pattacini L, Valdre L, Fagioli M, et al. Nuclear factor-erythroid 2 (NF-E2) expression in normal and malignant megakaryocytopoiesis. Leukemia. 2002;16:1773-81 pubmed
    ..These two findings provide strong indirect evidence of altered activity of the a isoform of NF-E2 in malignant megakaryocytes, raising the possibility that NF-E2 could play a role in megakaryocyte transformation. ..
  29. Moran J, Dahl E, Mulcahy R. Differential induction of mafF, mafG and mafK expression by electrophile-response-element activators. Biochem J. 2002;361:371-7 pubmed
  30. Shimokawa N, Kumaki I, Takayama K. MafG-2 is a novel Maf protein that is expressed by stimulation of extracellular H(+). Cell Signal. 2001;13:835-9 pubmed
    ..These results suggest that an increase in extracellular proton may induce the expression of mafG-2 mRNA and MafG-2 may be involved in signal transduction of extracellular of H(+). ..
  31. Motohashi H, Fujita R, Takayama M, Inoue A, Katsuoka F, Bresnick E, et al. Molecular determinants for small Maf protein control of platelet production. Mol Cell Biol. 2011;31:151-62 pubmed publisher
    ..These results demonstrate that the MafG C terminus is required for NF-E2 function and suggest that efficient targeting of NF-E2 to a specific nuclear scaffold is important to achieve high-level activity. ..
  32. Hirotsu Y, Katsuoka F, Funayama R, Nagashima T, Nishida Y, Nakayama K, et al. Nrf2-MafG heterodimers contribute globally to antioxidant and metabolic networks. Nucleic Acids Res. 2012;40:10228-39 pubmed publisher
    ..These data clearly support the notion that Nrf2-sMaf heterodimers are complexes that regulate batteries of genes involved in various aspects of cytoprotective and metabolic functions through associated AREs. ..