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Gene Review

Zfpm2  -  zinc finger protein, multitype 2

Mus musculus

Synonyms: B330005D23Rik, FOG-2, FOG2, Fog2, Friend of GATA 2, ...
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Disease relevance of Zfpm2


High impact information on Zfpm2


Biological context of Zfpm2


Anatomical context of Zfpm2

  • We found that Sry transcript levels were significantly reduced in XY Fog2(-/-) gonads at E11.5, which is the time when Sry expression normally reaches its peak [9].
  • Mouse fetuses homozygous for a null allele of Fog2 or homozygous for a targeted mutation in Gata4 (Gata4(ki)) that abrogates the interaction of GATA4 with FOG co-factors exhibit abnormalities in gonadogenesis [9].
  • 5. The other member of the mammalian FOG family, FOG-2, was not detected in gastric epithelium [10].
  • The interaction between COUP-TF2 and FOG-2 in mammalian cells was confirmed by co-immunoprecipitation of these proteins from transfected COS-7 cells [5].
  • We describe a novel FOG-related factor, FOG-2, that is expressed predominantly in the developing and adult heart, brain, and testis [6].

Associations of Zfpm2 with chemical compounds

  • Fog2 (Zfpm2) maps within the recombinant interval carrying the N-ethyl-N-nitrosourea-induced mutation, and DNA sequencing of Fog2 identified a mutation in a splice donor site that generates an abnormal transcript encoding a truncated protein [11].

Regulatory relationships of Zfpm2

  • Zfpm2 (also known as Fog-2) is a multi-zinc-finger protein that is co-expressed with Gata4 in the developing heart beginning at E8.5 (refs 8-10) [1].

Other interactions of Zfpm2

  • Gonadal differentiation, sex determination and normal Sry expression in mice require direct interaction between transcription partners GATA4 and FOG2 [9].
  • Full-length FOG-2 markedly enhanced transcriptional repression by GAL4-COUP-TF2(117-414), but not by a COUP-TF2 repression domain mutant [5].
  • Further transient-transfection assays of various mutant promoters established the functional relevance of the Gata4-response and unknown factor-response elements, while studies of Dmrt1 expression in 13.5 days postcoitum Fog2 null gonads supported the in vivo importance of Gata4's regulation [12].
  • Friend of GATA-1 (FOG-1) interacts with GATA-1 and is expressed principally in hematopoietic lineages, whereas FOG-2 is expressed predominantly in heart and brain [13].
  • Remarkably, though FOG-2 is quite divergent from FOG in its primary sequence, forced expression of FOG-2 rescues terminal erythroid maturation of FOG-/- hematopoietic cells [14].


  1. A syndrome of tricuspid atresia in mice with a targeted mutation of the gene encoding Fog-2. Svensson, E.C., Huggins, G.S., Lin, H., Clendenin, C., Jiang, F., Tufts, R., Dardik, F.B., Leiden, J.M. Nat. Genet. (2000) [Pubmed]
  2. Proper coronary vascular development and heart morphogenesis depend on interaction of GATA-4 with FOG cofactors. Crispino, J.D., Lodish, M.B., Thurberg, B.L., Litovsky, S.H., Collins, T., Molkentin, J.D., Orkin, S.H. Genes Dev. (2001) [Pubmed]
  3. FOG-2, a cofactor for GATA transcription factors, is essential for heart morphogenesis and development of coronary vessels from epicardium. Tevosian, S.G., Deconinck, A.E., Tanaka, M., Schinke, M., Litovsky, S.H., Izumo, S., Fujiwara, Y., Orkin, S.H. Cell (2000) [Pubmed]
  4. Endothelial lineage-mediated loss of the GATA cofactor Friend of GATA 1 impairs cardiac development. Katz, S.G., Williams, A., Yang, J., Fujiwara, Y., Tsang, A.P., Epstein, J.A., Orkin, S.H. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  5. Friend of GATA 2 physically interacts with chicken ovalbumin upstream promoter-TF2 (COUP-TF2) and COUP-TF3 and represses COUP-TF2-dependent activation of the atrial natriuretic factor promoter. Huggins, G.S., Bacani, C.J., Boltax, J., Aikawa, R., Leiden, J.M. J. Biol. Chem. (2001) [Pubmed]
  6. FOG-2, a heart- and brain-enriched cofactor for GATA transcription factors. Lu, J.R., McKinsey, T.A., Xu, H., Wang, D.Z., Richardson, J.A., Olson, E.N. Mol. Cell. Biol. (1999) [Pubmed]
  7. FOG-2 attenuates endothelial-to-mesenchymal transformation in the endocardial cushions of the developing heart. Flagg, A.E., Earley, J.U., Svensson, E.C. Dev. Biol. (2007) [Pubmed]
  8. Friend of GATA (FOG)-1 and FOG-2 differentially repress the GATA-dependent activity of multiple gonadal promoters. Robert, N.M., Tremblay, J.J., Viger, R.S. Endocrinology (2002) [Pubmed]
  9. Gonadal differentiation, sex determination and normal Sry expression in mice require direct interaction between transcription partners GATA4 and FOG2. Tevosian, S.G., Albrecht, K.H., Crispino, J.D., Fujiwara, Y., Eicher, E.M., Orkin, S.H. Development (2002) [Pubmed]
  10. GATA-4:FOG interactions regulate gastric epithelial development in the mouse. Jacobsen, C.M., Mannisto, S., Porter-Tinge, S., Genova, E., Parviainen, H., Heikinheimo, M., Adameyko, I.I., Tevosian, S.G., Wilson, D.B. Dev. Dyn. (2005) [Pubmed]
  11. Fog2 is required for normal diaphragm and lung development in mice and humans. Ackerman, K.G., Herron, B.J., Vargas, S.O., Huang, H., Tevosian, S.G., Kochilas, L., Rao, C., Pober, B.R., Babiuk, R.P., Epstein, J.A., Greer, J.J., Beier, D.R. PLoS Genet. (2005) [Pubmed]
  12. Gata4 regulates testis expression of Dmrt1. Lei, N., Heckert, L.L. Mol. Cell. Biol. (2004) [Pubmed]
  13. FOG acts as a repressor of red blood cell development in Xenopus. Deconinck, A.E., Mead, P.E., Tevosian, S.G., Crispino, J.D., Katz, S.G., Zon, L.I., Orkin, S.H. Development (2000) [Pubmed]
  14. FOG-2: A novel GATA-family cofactor related to multitype zinc-finger proteins Friend of GATA-1 and U-shaped. Tevosian, S.G., Deconinck, A.E., Cantor, A.B., Rieff, H.I., Fujiwara, Y., Corfas, G., Orkin, S.H. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
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