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Gene Review

Foxk1  -  forkhead box K1

Mus musculus

Synonyms: A630048H08Rik, AI463295, ENSMUSG00000075577, Forkhead box protein K1, Gm10868, ...
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Disease relevance of Foxk1


High impact information on Foxk1

  • Myogenic stem cell function is impaired in mice lacking the forkhead/winged helix protein MNF [1].
  • Skeletal muscles of Mnf-/- animals are atrophic, and satellite cell function is impaired [1].
  • Haploinsufficiency at the Mnf locus (Mnf+/-) also exacerbates the mdx phenotype to more closely resemble Duchenne's muscular dystrophy in humans [1].
  • A novel winged-helix transcription factor, MNF-beta, is expressed coincidentally with cell cycle withdrawal and differentiation of skeletal myogenic cells [4].
  • Transient expression of a winged-helix protein, MNF-beta, during myogenesis [4].

Biological context of Foxk1

  • Here we show that myogenic progenitor cells from Foxk1-/- mice are reduced in number and have perturbed cell cycle progression (G(0)/G(1) arrest) [5].
  • Mnf mutant mice were intercrossed with mdx mice that lack dystrophin and exhibit only a subtle myopathic phenotype [1].
  • A DNA sequence motif binding MNF-beta with high affinity was selected from a library of random oligonucleotides and was found to be similar to but distinct from the cognate binding site for HNF-3beta, a more distantly related winged-helix protein [4].
  • Transcriptional repression by MNF-beta-mSin3 complexes may contribute to the co-ordination of cellular proliferation and terminal differentiation of myogenic precursor cells [6].
  • 1. Foxk1 gene, consisting of nine exons, was mapped to mouse chromosome 5G2 [7].

Anatomical context of Foxk1

  • Absence of p21CIP rescues myogenic progenitor cell proliferative and regenerative capacity in Foxk1 null mice [5].
  • Foxk1 is a forkhead/winged helix transcription factor that is restricted to myogenic progenitor cells in adult skeletal muscle [5].
  • Probes based on this sequence identify two mRNA species that are upregulated during myocyte differentiation, and antibodies raised against recombinant MNF identify proteins of approximately 90, 68, and 65 kDa whose expression is regulated following differentiation of myogenic cells in culture [8].
  • MNF also is expressed selectively but transiently at embryonic stages of myogenesis in the developing myotome, limb bud precursors, and heart tube, but by late fetal stages of development, MNF is down-regulated within differentiated cardiac and skeletal myocytes, and persistently high expression is observed only in satellite cells [9].
  • Recent studies identified muscle transcription factors like MEF-2, TEF-1 and MNF, which are common to both the skeletal and cardiac muscle lineages [10].

Associations of Foxk1 with chemical compounds


Regulatory relationships of Foxk1


  1. Myogenic stem cell function is impaired in mice lacking the forkhead/winged helix protein MNF. Garry, D.J., Meeson, A., Elterman, J., Zhao, Y., Yang, P., Bassel-Duby, R., Williams, R.S. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  2. Insulin-like growth factor (IGF-I) induces myotube hypertrophy associated with an increase in anaerobic glycolysis in a clonal skeletal-muscle cell model. Semsarian, C., Sutrave, P., Richmond, D.R., Graham, R.M. Biochem. J. (1999) [Pubmed]
  3. A new mechanism of action of dipyrone: blockade of the release of a nociceptive factor from macrophages. de Campos, D.I., Cunha, F.Q., Ferreira, S.H. Braz. J. Med. Biol. Res. (1988) [Pubmed]
  4. Transient expression of a winged-helix protein, MNF-beta, during myogenesis. Yang, Q., Bassel-Duby, R., Williams, R.S. Mol. Cell. Biol. (1997) [Pubmed]
  5. Absence of p21CIP rescues myogenic progenitor cell proliferative and regenerative capacity in Foxk1 null mice. Hawke, T.J., Jiang, N., Garry, D.J. J. Biol. Chem. (2003) [Pubmed]
  6. The winged-helix/forkhead protein myocyte nuclear factor beta (MNF-beta) forms a co-repressor complex with mammalian sin3B. Yang, Q., Kong, Y., Rothermel, B., Garry, D.J., Bassel-Duby, R., Williams, R.S. Biochem. J. (2000) [Pubmed]
  7. Identification and characterization of human FOXK1 gene in silico. Katoh, M., Katoh, M. Int. J. Mol. Med. (2004) [Pubmed]
  8. Myocyte nuclear factor, a novel winged-helix transcription factor under both developmental and neural regulation in striated myocytes. Bassel-Duby, R., Hernandez, M.D., Yang, Q., Rochelle, J.M., Seldin, M.F., Williams, R.S. Mol. Cell. Biol. (1994) [Pubmed]
  9. Persistent expression of MNF identifies myogenic stem cells in postnatal muscles. Garry, D.J., Yang, Q., Bassel-Duby, R., Williams, R.S. Dev. Biol. (1997) [Pubmed]
  10. Transcription factors and the cardiac gene programme. Doevendans, P.A., van Bilsen, M. Int. J. Biochem. Cell Biol. (1996) [Pubmed]
  11. Identification of a myocyte nuclear factor that binds to the muscle-specific enhancer of the mouse muscle creatine kinase gene. Buskin, J.N., Hauschka, S.D. Mol. Cell. Biol. (1989) [Pubmed]
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