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Gene Review

Ebf1  -  early B cell factor 1

Mus musculus

Synonyms: AW990631, Coe1, Early B-cell factor, Ebf, O/E-1, ...
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Disease relevance of Ebf1


High impact information on Ebf1

  • Early B-cell factor (EBF) is a cell type-specific transcription factor that is expressed at all antigen-independent stages of B-lymphocyte differentiation and participates in the regulation of the mb-1 gene [3].
  • EBF-deficient mice lack B cells that have rearranged their immunoglobulin D and JH gene segments, but contain B220+CD43+ progenitor cells that express germline mu and IL-7 receptor transcripts [3].
  • Together, these data suggest that EBF plays a specific and important role in the transcriptional control of B-cell differentiation at a stage before Ig (immunoglobulin) gene rearrangement but after commitment of cells to the B-lymphoid lineage [3].
  • Cloning and functional characterization of early B-cell factor, a regulator of lymphocyte-specific gene expression [4].
  • Partial amino acid sequences obtained from purified EBF were used to isolate cDNA clones, which by multiple criteria encode EBF [4].
  • Functional analysis on mice lacking the VM-specific gene early B-cell factor 1 (Ebf1) revealed that Ebf1 is essential for the terminal migration of mDA neurons in the substantia nigra pars compacta [5].

Biological context of Ebf1

  • Here we show that Ebf1 controls cell differentiation in the murine embryonic striatum, where it is the only gene of the family to be expressed [6].
  • Furthermore, the PyG box binds to a factor in nuclear extracts from human B-cell lines that also interact with the mouse mb-1 promoter EBF binding site [7].
  • Expression of recombinant EBF in transfected nonlymphoid cells strongly activated transcription from reporter plasmids containing functional EBF-binding sites [4].
  • Multiple functionally important EBF and E47 binding sites were identified in the lambda5 promoter/enhancer region, indicating that lambda5 is a direct genetic target for these transcription factors [8].
  • We found that the conversion of 70Z/3 pre-B lymphocytes to cells with a macrophage-like phenotype is associated with the loss of E2A and EBF [9].

Anatomical context of Ebf1

  • Phenotypic and expression studies show that Bcl11a functions upstream of the transcription factors Ebf1 and Pax5 in the B cell pathway [10].
  • Our data therefore show that Ebf1 plays an essential role in the acquisition of mantle cell molecular identity in the developing striatum and provide information on the genetic hierarchies that govern neuronal differentiation in the ventral telencephalon [6].
  • To address this issue, we examined Ebf1(-/-) embryos in which a subset of thalamic axons does not reach the neocortex [11].
  • This shift is first detected inside the basal ganglia, a structure on the path of thalamic axons, and which develops abnormally in Ebf1(-/-) embryos [11].
  • We also obtained evidence for extensive collaborative actions of EBF and E47 even though microarray analysis of hematopoetic progenitor cells ectopically expressing these proteins suggested that they activated only a subset of pre-B cell restricted genes [12].

Associations of Ebf1 with chemical compounds

  • By using gene knockout techniques it has been found that mice carrying a targeted deletion of Ebf2 gene, a component of Olf/Ebf bHLH transcription factors, show a defective migration of GnRH neurons, providing the first evidence of a mouse model of such defect [13].

Physical interactions of Ebf1


Regulatory relationships of Ebf1


Other interactions of Ebf1

  • EBF function was enhanced by interaction with the transcription factor Runx1 [21].
  • These results indicate that IL-7 directs commitment of CLPs by modulating EBF expression [22].
  • The early topography of thalamocortical projections is shifted in Ebf1 and Dlx1/2 mutant mice [11].
  • Therefore, high levels of E protein activity are essential for the activation of EBF and N-myc, whereas lower levels of E protein activity, in synergy with other B lineage transcription factors, are sufficient for expression of most B lineage genes [23].
  • These data suggest that the B29 gene is a genetic target for EBF in early B-cell development [14].

Analytical, diagnostic and therapeutic context of Ebf1

  • Recombinant mouse EBF binds to the PyG site with an affinity about 3-fold lower than to the EBF binding site from the mouse mb-1 promoter in electrophoretic mobility shift assays [7].
  • These sites were important for the full function of the promoter in a preB cell line, and chromatin immunoprecipitation experiments indicate that EBF interacts with the promoter in vivo [24].


  1. Early B cell factor interacts with a subset of kappa promoters. Sigvardsson, M., Akerblad, P., Leanderson, T. J. Immunol. (1996) [Pubmed]
  2. Early B-cell factor-associated zinc-finger gene is a frequent target of retroviral integration in murine B-cell lymphomas. Warming, S., Suzuki, T., Yamaguchi, T.P., Jenkins, N.A., Copeland, N.G. Oncogene (2004) [Pubmed]
  3. Failure of B-cell differentiation in mice lacking the transcription factor EBF. Lin, H., Grosschedl, R. Nature (1995) [Pubmed]
  4. Cloning and functional characterization of early B-cell factor, a regulator of lymphocyte-specific gene expression. Hagman, J., Belanger, C., Travis, A., Turck, C.W., Grosschedl, R. Genes Dev. (1993) [Pubmed]
  5. Ventral mesencephalon-enriched genes that regulate the development of dopaminergic neurons in vivo. Yin, M., Liu, S., Yin, Y., Li, S., Li, Z., Wu, X., Zhang, B., Ang, S.L., Ding, Y., Zhou, J. J. Neurosci. (2009) [Pubmed]
  6. Ebf1 controls early cell differentiation in the embryonic striatum. Garel, S., Marín, F., Grosschedl, R., Charnay, P. Development (1999) [Pubmed]
  7. A human early B-cell factor-like protein participates in the regulation of the human CD19 promoter. Gisler, R., Akerblad, P., Sigvardsson, M. Mol. Immunol. (1999) [Pubmed]
  8. EBF and E47 collaborate to induce expression of the endogenous immunoglobulin surrogate light chain genes. Sigvardsson, M., O'Riordan, M., Grosschedl, R. Immunity (1997) [Pubmed]
  9. Induction of early B cell factor (EBF) and multiple B lineage genes by the basic helix-loop-helix transcription factor E12. Kee, B.L., Murre, C. J. Exp. Med. (1998) [Pubmed]
  10. Bcl11a is essential for normal lymphoid development. Liu, P., Keller, J.R., Ortiz, M., Tessarollo, L., Rachel, R.A., Nakamura, T., Jenkins, N.A., Copeland, N.G. Nat. Immunol. (2003) [Pubmed]
  11. The early topography of thalamocortical projections is shifted in Ebf1 and Dlx1/2 mutant mice. Garel, S., Yun, K., Grosschedl, R., Rubenstein, J.L. Development (2002) [Pubmed]
  12. Pearson correlation analysis of microarray data allows for the identification of genetic targets for early B-cell factor. Månsson, R., Tsapogas, P., Akerlund, M., Lagergren, A., Gisler, R., Sigvardsson, M. J. Biol. Chem. (2004) [Pubmed]
  13. Factors involved in the migration of neuroendocrine hypothalamic neurons. Maggi, R., Cariboni, A., Zaninetti, R., Samara, A., Stossi, F., Pimpinelli, F., Giacobini, P., Consalez, G.G., Rugarli, E., Piva, F. Archives italiennes de biologie. (2005) [Pubmed]
  14. The B29 (immunoglobulin beta-chain) gene is a genetic target for early B-cell factor. Akerblad, P., Rosberg, M., Leanderson, T., Sigvardsson, M. Mol. Cell. Biol. (1999) [Pubmed]
  15. The lambda5-VpreB1 locus--a model system for studying gene regulation during early B cell development. Sabbattini, P., Dillon, N. Semin. Immunol. (2005) [Pubmed]
  16. DNA binding and transcriptional activation by the Ski oncoprotein mediated by interaction with NFI. Tarapore, P., Richmond, C., Zheng, G., Cohen, S.B., Kelder, B., Kopchick, J., Kruse, U., Sippel, A.E., Colmenares, C., Stavnezer, E. Nucleic Acids Res. (1997) [Pubmed]
  17. Early B-cell factor (EBF) down-regulates immunoglobulin heavy chain intron enhancer function in a plasmacytoma cell line. Akerblad, P., Sigvardsson, M., Leanderson, T. Scand. J. Immunol. (1996) [Pubmed]
  18. The human prepro-orexin gene regulatory region that activates gene expression in the lateral region and represses it in the medial regions of the hypothalamus. Moriguchi, T., Sakurai, T., Takahashi, S., Goto, K., Yamamoto, M. J. Biol. Chem. (2002) [Pubmed]
  19. Role of Olf-1 and Pax-6 transcription factors in neurodevelopment. Davis, J.A., Reed, R.R. J. Neurosci. (1996) [Pubmed]
  20. Early B cell factor is an activator of the B lymphoid kinase promoter in early B cell development. Akerblad, P., Sigvardsson, M. J. Immunol. (1999) [Pubmed]
  21. Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription. Maier, H., Ostraat, R., Gao, H., Fields, S., Shinton, S.A., Medina, K.L., Ikawa, T., Murre, C., Singh, H., Hardy, R.R., Hagman, J. Nat. Immunol. (2004) [Pubmed]
  22. Interleukin-7 is necessary to maintain the B cell potential in common lymphoid progenitors. Dias, S., Silva, H., Cumano, A., Vieira, P. J. Exp. Med. (2005) [Pubmed]
  23. Early B cell factor promotes B lymphopoiesis with reduced interleukin 7 responsiveness in the absence of E2A. Seet, C.S., Brumbaugh, R.L., Kee, B.L. J. Exp. Med. (2004) [Pubmed]
  24. The human V-preB promoter is a target for coordinated activation by early B cell factor and E47. Gisler, R., Sigvardsson, M. J. Immunol. (2002) [Pubmed]
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