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Klf1  -  Kruppel-like factor 1 (erythroid)

Mus musculus

Synonyms: EKLF, Eklf, Elkf, Erythroid krueppel-like transcription factor, Krueppel-like factor 1, ...
 
 
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Disease relevance of Klf1

  • Retroviral integration within the Fli-2 locus results in inactivation of the erythroid transcription factor NF-E2 in Friend erythroleukemias: evidence that NF-E2 is essential for globin expression [1].
  • Despite efficient production of hybrid malpha(2)-hgamma(2) hemoglobin in the fetal livers of EKLF(-/-) animals, hemolysis was not corrected and survival was not prolonged [2].
  • These results suggest that strategies designed to antagonize EKLF function in adults with hemoglobinopathy, in an attempt to reactivate gamma-globin gene expression, may adversely affect other essential aspects of red blood cell physiology [2].
  • Transactivation of erythroid transcription factor GATA-1 by a myb-ets-containing retrovirus [3].
 

High impact information on Klf1

  • These acetyltransferases also modify certain transcription factors (TFIIEbeta, TFIIF, EKLF and p53) [4].
  • Lethal beta-thalassaemia in mice lacking the erythroid CACCC-transcription factor EKLF [5].
  • Erythroid transcription factor GATA-1 is abundantly transcribed in mouse testis [6].
  • Blood ASCs also express higher amounts of Kruppel-like factor (KLF)2, a regulator of S1P(1) gene expression [7].
  • This suggests that EKLF interacts directly with the CACC motifs in 5'HS3 and demonstrates that EKLF is also a transcriptional activator in embryonic erythropoiesis [8].
 

Biological context of Klf1

 

Anatomical context of Klf1

 

Associations of Klf1 with chemical compounds

  • Regulation of the erythroid transcription factor NF-E2 by cyclic adenosine monophosphate-dependent protein kinase [17].
  • Estrogen-induced apoptosis by inhibition of the erythroid transcription factor GATA-1 [18].
  • Here, we demonstrate that the erythroid transcription factor GATA-1 is sumoylated in vitro and in vivo and map the single lysine residue involved in SUMO-1 attachment [19].
  • The Krüppel-like factor KLF15 regulates the insulin-sensitive glucose transporter GLUT4 [20].
 

Physical interactions of Klf1

 

Regulatory relationships of Klf1

  • The EKLF promoter can be directly activated in nonerythroid cells in cotransfection experiments by forced expression of GATA-1 [9].
  • While EKLF is expressed exclusively in erythroid cells, LKLF is expressed temporally during early embryonic development and predominantly in the adult mouse lung [10].
 

Other interactions of Klf1

  • We have shown that GATA-1 interacts physically with Sp1 and EKLF and that interactions are mediated through their respective DNA-binding domains [22].
  • Expression of other erythroid specific genes such as EKLF, GATA1 and GATA3 is unaltered in these animals [10].
  • Nevertheless, expression of the beta-minor globin gene in EKLF KO mice has not been assessed to date [23].
  • The results obtained support a general role of EKLF in beta-globin gene activation and are in agreement with models involving an advantage of the LCR proximal respect to distal gene [23].
  • EBs were competent to respond to BMP4 only until day 4 of differentiation, which coincides with the normal onset of EKLF expression [24].
 

Analytical, diagnostic and therapeutic context of Klf1

References

  1. Retroviral integration within the Fli-2 locus results in inactivation of the erythroid transcription factor NF-E2 in Friend erythroleukemias: evidence that NF-E2 is essential for globin expression. Lu, S.J., Rowan, S., Bani, M.R., Ben-David, Y. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  2. Fetal expression of a human Agamma globin transgene rescues globin chain imbalance but not hemolysis in EKLF null mouse embryos. Perkins, A.C., Peterson, K.R., Stamatoyannopoulos, G., Witkowska, H.E., Orkin, S.H. Blood (2000) [Pubmed]
  3. Transactivation of erythroid transcription factor GATA-1 by a myb-ets-containing retrovirus. Aurigemma, R.E., Blair, D.G., Ruscetti, S.K. J. Virol. (1992) [Pubmed]
  4. Regulation of activity of the transcription factor GATA-1 by acetylation. Boyes, J., Byfield, P., Nakatani, Y., Ogryzko, V. Nature (1998) [Pubmed]
  5. Lethal beta-thalassaemia in mice lacking the erythroid CACCC-transcription factor EKLF. Perkins, A.C., Sharpe, A.H., Orkin, S.H. Nature (1995) [Pubmed]
  6. Erythroid transcription factor GATA-1 is abundantly transcribed in mouse testis. Ito, E., Toki, T., Ishihara, H., Ohtani, H., Gu, L., Yokoyama, M., Engel, J.D., Yamamoto, M. Nature (1993) [Pubmed]
  7. Plasma cell S1P1 expression determines secondary lymphoid organ retention versus bone marrow tropism. Kabashima, K., Haynes, N.M., Xu, Y., Nutt, S.L., Allende, M.L., Proia, R.L., Cyster, J.G. J. Exp. Med. (2006) [Pubmed]
  8. Erythroid Krüppel-like factor (EKLF) is active in primitive and definitive erythroid cells and is required for the function of 5'HS3 of the beta-globin locus control region. Tewari, R., Gillemans, N., Wijgerde, M., Nuez, B., von Lindern, M., Grosveld, F., Philipsen, S. EMBO J. (1998) [Pubmed]
  9. Regulation of the erythroid Kruppel-like factor (EKLF) gene promoter by the erythroid transcription factor GATA-1. Crossley, M., Tsang, A.P., Bieker, J.J., Orkin, S.H. J. Biol. Chem. (1994) [Pubmed]
  10. Loss of LKLF function results in embryonic lethality in mice. Wani, M.A., Means, R.T., Lingrel, J.B. Transgenic Res. (1998) [Pubmed]
  11. Multiple proteins binding to a GATA-E box-GATA motif regulate the erythroid Krüppel-like factor (EKLF) gene. Anderson, K.P., Crable, S.C., Lingrel, J.B. J. Biol. Chem. (1998) [Pubmed]
  12. Developmental regulation of yolk sac hematopoiesis by Kruppel-like factor 6. Matsumoto, N., Kubo, A., Liu, H., Akita, K., Laub, F., Ramirez, F., Keller, G., Friedman, S.L. Blood (2006) [Pubmed]
  13. A shortened life span of EKLF-/- adult erythrocytes, due to a deficiency of beta-globin chains, is ameliorated by human gamma-globin chains. Lim, S.K., Bieker, J.J., Lin, C.S., Costantini, F. Blood (1997) [Pubmed]
  14. Erythroid Kruppel-like factor (EKLF) coordinates erythroid cell proliferation and hemoglobinization in cell lines derived from EKLF null mice. Coghill, E., Eccleston, S., Fox, V., Cerruti, L., Brown, C., Cunningham, J., Jane, S., Perkins, A. Blood (2001) [Pubmed]
  15. The erythroid phenotype of EKLF-null mice: defects in hemoglobin metabolism and membrane stability. Drissen, R., von Lindern, M., Kolbus, A., Driegen, S., Steinlein, P., Beug, H., Grosveld, F., Philipsen, S. Mol. Cell. Biol. (2005) [Pubmed]
  16. A novel, erythroid cell-specific murine transcription factor that binds to the CACCC element and is related to the Krüppel family of nuclear proteins. Miller, I.J., Bieker, J.J. Mol. Cell. Biol. (1993) [Pubmed]
  17. Regulation of the erythroid transcription factor NF-E2 by cyclic adenosine monophosphate-dependent protein kinase. Casteel, D., Suhasini, M., Gudi, T., Naima, R., Pilz, R.B. Blood (1998) [Pubmed]
  18. Estrogen-induced apoptosis by inhibition of the erythroid transcription factor GATA-1. Blobel, G.A., Orkin, S.H. Mol. Cell. Biol. (1996) [Pubmed]
  19. Modification of the erythroid transcription factor GATA-1 by SUMO-1. Collavin, L., Gostissa, M., Avolio, F., Secco, P., Ronchi, A., Santoro, C., Del Sal, G. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  20. The Krüppel-like factor KLF15 regulates the insulin-sensitive glucose transporter GLUT4. Gray, S., Feinberg, M.W., Hull, S., Kuo, C.T., Watanabe, M., Sen-Banerjee, S., DePina, A., Haspel, R., Jain, M.K. J. Biol. Chem. (2002) [Pubmed]
  21. Chromatin-binding in vivo of the erythroid kruppel-like factor, EKLF, in the murine globin loci. Shyu, Y.C., Wen, S.C., Lee, T.L., Chen, X., Hsu, C.T., Chen, H., Chen, R.L., Hwang, J.L., Shen, C.K. Cell Res. (2006) [Pubmed]
  22. Functional synergy and physical interactions of the erythroid transcription factor GATA-1 with the Krüppel family proteins Sp1 and EKLF. Merika, M., Orkin, S.H. Mol. Cell. Biol. (1995) [Pubmed]
  23. beta-Minor globin gene expression is preferentially reduced in EKLF Knock-Out mice. Porcu, S., Poddie, D., Melis, M., Cao, A., Ristaldi, M.S. Gene (2005) [Pubmed]
  24. The BMP/BMPR/Smad pathway directs expression of the erythroid-specific EKLF and GATA1 transcription factors during embryoid body differentiation in serum-free media. Adelman, C.A., Chattopadhyay, S., Bieker, J.J. Development (2002) [Pubmed]
  25. Erythroid Krüppel-like factor exhibits an early and sequentially localized pattern of expression during mammalian erythroid ontogeny. Southwood, C.M., Downs, K.M., Bieker, J.J. Dev. Dyn. (1996) [Pubmed]
 
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