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EBF1  -  early B-cell factor 1

Homo sapiens

Synonyms: COE1, EBF, Early B-cell factor, O/E-1, OE-1, ...
 
 
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Disease relevance of EBF1

  • Axonal damage is a hallmark for multiple sclerosis clinical disability and EBF plays an evolutionarily conserved role in the expression of proteins essential for axonal pathfinding [1].
  • Indeed, transduction with an EBF-encoding retrovirus partly reactivated endogenous Pax5 [2].
  • METHODS: To investigate this selectivity in target gene activation we compared the overall gene expression patterns by micro-array analysis and expression of target genes for the transcription factor EBF in lymphoma and neuroblastoma cells by RT-PCR [3].
  • To obtain further insight into the molecular processes involved in the formation of these tumors, we decided to investigate the functional role of Olf/EBF (O/E) transcription factors in human neuroblastoma cells [4].
  • Through the use of novel biological network analyses, essential regulators of early B cell development, PAX5 and EBF, were shown to be associated with a clear B-lineage commitment in lymphoblastic t(11q23)/MLL leukemias [5].
 

High impact information on EBF1

 

Chemical compound and disease context of EBF1

 

Biological context of EBF1

  • Distinct promoters mediate the regulation of ebf1 gene expression by interleukin-7 and pax5 [11].
  • Taken together, these data suggest that the regulation of Ebf1 via distinct promoters allows for the generation of several feedback loops and the coordination of multiple determinants of B lymphopoiesis in a regulatory network [11].
  • 1. This promoter contains 5 independent binding sites capable of interacting with hEBF in the EMSA, and the activity of the promoter was induced 24-fold in co-transfection experiments [12].
  • A trend for association in the case-control study of another EBF1 marker, the allele 5 of the very informative microsatellite D5S2038, was corroborated by Transmission Disequilibrium Test of 53 trios (p = 0.03) [1].
  • Two genetic markers within the EBF1 gene have been found associated with this neurological disease, indicative either of their causative role or that of some other polymorphism in linkage disequilibrium with them [1].
 

Anatomical context of EBF1

  • Inhibition of EBF function by active Notch signaling reveals a novel regulatory pathway in early B-cell development [13].
  • The EBF/Olf/Collier family of transcription factors: regulators of differentiation in cells originating from all three embryonal germ layers [14].
  • It is also shown that EBF-binding sites are functionally conserved in the human mb-1 and B29 promoters because hEBF interacts with these in the electrophoretic mobility shift assay (EMSA) and have the ability to increase the activity of reporter constructs under the control of these promoters in nonlymphoid HeLa cells [12].
  • Early B cell factor (EBF) was identified and cloned as a transcription factor expressed specifically in B lymphocytes and adipocytes [9].
  • Reduction of Ebf1 and Ebf2 proteins by specific short hairpin RNA blocks differentiation of 3T3-L1 cells, suggesting a critical role for these factors and the absence of functional redundancy between members of this family [15].
 

Associations of EBF1 with chemical compounds

  • Deletion analysis and transfer of regions of EBF onto a heterologous DNA binding domain identified a serine/threonine-rich transcriptional activation domain [9].
  • Furthermore, we find that the ethylene insensitivity of ein5 mutant plants is a consequence of the over-accumulation of EBF1 and EBF2 mRNAs resulting in the under-accumulation of EIN3 even in the presence of ethylene gas [16].
  • EBF recognizes the nucleotide sequence 5'-CAAGGGAAT-3' in the mb-1 and major histocompatibility complex (MHC) class II A alpha d promoters [17].
  • The EBF is defined as the ratio of the ionization with the backscatterer to the ionization with a full polystyrene medium, and is approximated by the ratio of the doses computed at the depth of the cavity [18].
  • Moreover, a distance of 3.1 A between the sulfur atom and the OE1 of Glu(143) suggests that they are H-bonded and that one of these atoms is protonated [19].
 

Regulatory relationships of EBF1

  • RESULTS: In pre-B cells mb-1 and CD19 are regulate by EBF-1 in collaboration with Pax-5 and E-proteins [3].
 

Other interactions of EBF1

  • These data suggest that Notch signaling may affect B-versus T-lineage commitment by the targeting of both EBF and E2A [13].
  • Failure of B-cell differentiation was found in EBF-deficient mice and involvement of B-lymphocytes in MS has been suggested from their presence in cerebrospinal fluid and lesions of patients [1].
  • Critical role for ebf1 and ebf2 in the adipogenic transcriptional cascade [15].
  • The transcription factor EBF can bypass the requirement for PU.1 and E2A in early B cell development [20].
  • Here we report that these three proteins have adipogenic potential in multiple cellular models and that peroxisome proliferator-activated receptor gamma (PPARgamma) is required for this effect, at least in part due to direct activation of the PPARgamma1 promoter by Ebf1 [15].
 

Analytical, diagnostic and therapeutic context of EBF1

References

  1. Early B-cell Factor gene association with multiple sclerosis in the Spanish population. Martínez, A., Mas, A., de las Heras, V., Arroyo, R., Fernández-Arquero, M., de la Concha, E.G., Urcelay, E. BMC neurology [electronic resource]. (2005) [Pubmed]
  2. B-Lymphoma cells with epigenetic silencing of Pax5 trans-differentiate into macrophages, but not other hematopoietic lineages. Hodawadekar, S., Yu, D., Cozma, D., Freedman, B., Sunyer, O., Atchison, M.L., Thomas-Tikhonenko, A. Exp. Cell Res. (2007) [Pubmed]
  3. Neuroblastoma and pre-B lymphoma cells share expression of key transcription factors but display tissue restricted target gene expression. Lagergren, A., Manetopoulos, C., Axelson, H., Sigvardsson, M. BMC Cancer (2004) [Pubmed]
  4. Olf/EBF proteins are expressed in neuroblastoma cells: potential regulators of the Chromogranin A and SCG10 promoters. Persson, P., Manetopoulos, C., Lagergren, A., Nygren, J., Gisler, R., Axelson, H., Sigvardsson, M. Int. J. Cancer (2004) [Pubmed]
  5. New insights into MLL gene rearranged acute leukemias using gene expression profiling: shared pathways, lineage commitment, and partner genes. Kohlmann, A., Schoch, C., Dugas, M., Schnittger, S., Hiddemann, W., Kern, W., Haferlach, T. Leukemia (2005) [Pubmed]
  6. Transcriptional control of early B cell development. Busslinger, M. Annu. Rev. Immunol. (2004) [Pubmed]
  7. Constitutively active beta-catenin confers multilineage differentiation potential on lymphoid and myeloid progenitors. Baba, Y., Garrett, K.P., Kincade, P.W. Immunity (2005) [Pubmed]
  8. Transcription factors drive B cell development. Hagman, J., Lukin, K. Curr. Opin. Immunol. (2006) [Pubmed]
  9. EBF contains a novel zinc coordination motif and multiple dimerization and transcriptional activation domains. Hagman, J., Gutch, M.J., Lin, H., Grosschedl, R. EMBO J. (1995) [Pubmed]
  10. Thyroid blood flow and uptake of technetium-99m pertechnetate in Graves' disease. Sekuli??, V., Raji??, M., Vlajkovi??, M., Ili??, S., Bogi??evi??, M., Anti??, S., Dimi??, D. Hellenic journal of nuclear medicine (2006) [Pubmed]
  11. Distinct promoters mediate the regulation of ebf1 gene expression by interleukin-7 and pax5. Roessler, S., Gy??ry, I., Imhof, S., Spivakov, M., Williams, R.R., Busslinger, M., Fisher, A.G., Grosschedl, R. Mol. Cell. Biol. (2007) [Pubmed]
  12. Cloning of human early B-cell factor and identification of target genes suggest a conserved role in B-cell development in man and mouse. Gisler, R., Jacobsen, S.E., Sigvardsson, M. Blood (2000) [Pubmed]
  13. Inhibition of EBF function by active Notch signaling reveals a novel regulatory pathway in early B-cell development. Smith, E.M., Akerblad, P., Kadesch, T., Axelson, H., Sigvardsson, M. Blood (2005) [Pubmed]
  14. The EBF/Olf/Collier family of transcription factors: regulators of differentiation in cells originating from all three embryonal germ layers. Liberg, D., Sigvardsson, M., Akerblad, P. Mol. Cell. Biol. (2002) [Pubmed]
  15. Critical role for ebf1 and ebf2 in the adipogenic transcriptional cascade. Jimenez, M.A., Akerblad, P., Sigvardsson, M., Rosen, E.D. Mol. Cell. Biol. (2007) [Pubmed]
  16. Inaugural Article: ETHYLENE-INSENSITIVE5 encodes a 5'->3' exoribonuclease required for regulation of the EIN3-targeting F-box proteins EBF1/2. Olmedo, G., Guo, H., Gregory, B.D., Nourizadeh, S.D., Aguilar-Henonin, L., Li, H., An, F., Guzman, P., Ecker, J.R. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  17. A novel lineage-specific nuclear factor regulates mb-1 gene transcription at the early stages of B cell differentiation. Hagman, J., Travis, A., Grosschedl, R. EMBO J. (1991) [Pubmed]
  18. Simple calculation of the electron-backscatter factor. Tabata, T., Ito, R. Medical physics. (1992) [Pubmed]
  19. Crystal structures of alpha-mercaptoacyldipeptides in the thermolysin active site: structural parameters for a Zn monodentation or bidentation in metalloendopeptidases. Gaucher, J.F., Selkti, M., Tiraboschi, G., Prangé, T., Roques, B.P., Tomas, A., Fournié-Zaluski, M.C. Biochemistry (1999) [Pubmed]
  20. Genetic networks that regulate B lymphopoiesis. Medina, K.L., Singh, H. Curr. Opin. Hematol. (2005) [Pubmed]
  21. Purification of early-B-cell factor and characterization of its DNA-binding specificity. Travis, A., Hagman, J., Hwang, L., Grosschedl, R. Mol. Cell. Biol. (1993) [Pubmed]
  22. Evidence based breast-feeding promotion: the baby-friendly hospital initiative. Pérez-Escamilla, R. J. Nutr. (2007) [Pubmed]
  23. Do exclusively breast-fed infants require extra protein? Dewey, K.G., Cohen, R.J., Rivera, L.L., Canahuati, J., Brown, K.H. Pediatr. Res. (1996) [Pubmed]
  24. Longitudinal assessment of ovarian perifollicular and endometrial vascularity by power Doppler ultrasound in pregnant and non-pregnant cycles in the IVF setting. Shrestha, S.M., Costello, M.F., Sjoblom, P., McNally, G., Bennett, M.J., Steigrad, S.J., Hughes, G.J. J. Assist. Reprod. Genet. (2004) [Pubmed]
 
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