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Gene Review

Zeb1  -  zinc finger E-box binding homeobox 1

Mus musculus

Synonyms: 3110032K11Rik, AREB6, BZP, Delta EF1, MEB1, ...
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Disease relevance of Zeb1

  • BZP inhibited transcription of the herpes simplex virus thymidine kinase promoter when copies of the 9-bp target motif were linked in cis, suggesting that it functions as a transcriptional repressor [1].
  • We show expression of Zfhep in the mesenchyme of the palatal shelves, establishing concordance of expression with the reported cleft palate of the deltaEF1-null mice [2].
  • Binding of the transcription factor ZEB (NIL-2-a) to the negative regulatory element NRE-A plays a critical role in silencing IL-2 expression in the EL-4 cell line, a murine Th1-like lymphoma [3].

Psychiatry related information on Zeb1

  • This mechanism of active transcriptional repression distinguishes ZEB from other negative regulators of myogenesis (Id, Twist and I-mfa) that inhibit muscle differentiation by simply binding and inactivating myogenic factors [4].

High impact information on Zeb1

  • Lens-specific expression of the delta 1-crystallin gene is controlled by factors, such as delta EF1, binding to its enhancer sequences [5].
  • The relative affinity of ZEB versus myogenic bHLH proteins varies for E boxes in different genes such that ZEB would be displaced from different genes at distinct times as myogenic bHLH proteins accumulate during myogenesis, thus providing a mechanism to regulate temporal order of gene expression [4].
  • The p73 intronic fragment contains six consensus binding sites for transcriptional repressor ZEB, which binds these sites in vitro and in vivo [6].
  • Independent repressor domains in ZEB regulate muscle and T-cell differentiation [7].
  • BZP, a novel serum-responsive zinc finger protein that inhibits gene transcription [1].

Biological context of Zeb1

  • An alignment of the deduced amino-acid sequences of the putative functional domains of MEB1 with those from the human, hamster and chicken homologues reveals a dramatic degree of conservation [8].
  • The nucleotide sequence encoding an approx. 120-kDa transcriptional repressor (MEB1) was determined from a cDNA which was cloned from a mouse brain library [8].
  • Promoter analysis and RNase-protection assay indicated that the gene is driven by a G+C-rich promoter without a TATA box, and the transcription start points (tsp) cluster around 20 bp from the start codon located in exon 1. cDNA and genomic sequences of the mouse delta EF1 were cloned and compared with the chicken sequence [9].
  • We have investigated the expression pattern of Zfhep protein during mouse embryogenesis [2].
  • Mutation and cotransfection analyses indicated the existence of an activator which counteracts the action of delta EF1 in lens cells, probably through binding site competition [10].

Anatomical context of Zeb1

  • Zfhx1a was expressed in a cell population immediately adjacent to cartilage anlagen as well as in developing tendons [11].
  • BZP mRNA and immunoreactivity were detected in several established cell lines but were most abundant in hamster insulinoma (HIT) cells, the parental source of the cDNAs [1].
  • In mouse tissues, BZP mRNA and immunoreactivity were identified in cells of the endocrine pancreas, anterior pituitary, and central nervous system [1].
  • FOXO transcription factors cooperate with delta EF1 to activate growth suppressive genes in B lymphocytes [12].
  • Also, Zfhep is expressed as cells migrate from a narrow region of the pons VZ towards the trigeminal nucleus [2].

Associations of Zeb1 with chemical compounds

  • The transcription factor delta EF1 is a key player in estrogen-signaling cascades in vertebrates [13].

Other interactions of Zeb1

  • Zfhx1a and Zfhx1b mRNAs have non-overlapping expression domains during chick and mouse midgestation limb development [11].

Analytical, diagnostic and therapeutic context of Zeb1

  • Electrophoretic mobility shift assay (EMSA) in control EL-4 cells revealed a slower migrating band, previously identified as ZEB, and a faster migrating band [3].
  • Competitive RT-PCR analysis of mRNA indicated that VT did not reduce ZEB transcript levels [3].


  1. BZP, a novel serum-responsive zinc finger protein that inhibits gene transcription. Franklin, A.J., Jetton, T.L., Shelton, K.D., Magnuson, M.A. Mol. Cell. Biol. (1994) [Pubmed]
  2. Expression of Zfhep/deltaEF1 protein in palate, neural progenitors, and differentiated neurons. Darling, D.S., Stearman, R.P., Qi, Y., Qiu, M.S., Feller, J.P. Gene Expr. Patterns (2003) [Pubmed]
  3. Vomitoxin (deoxynivalenol)-mediated inhibition of nuclear protein binding to NRE-A, an IL-2 promoter negative regulatory element, in EL-4 cells. Yang, G.H., Pestka, J.J. Toxicology (2002) [Pubmed]
  4. ZEB, a vertebrate homolog of Drosophila Zfh-1, is a negative regulator of muscle differentiation. Postigo, A.A., Dean, D.C. EMBO J. (1997) [Pubmed]
  5. Gene regulation and differentiation in vertebrate ocular tissues. Kodama, R., Eguchi, G. Curr. Opin. Genet. Dev. (1994) [Pubmed]
  6. The transcriptional repressor ZEB regulates p73 expression at the crossroad between proliferation and differentiation. Fontemaggi, G., Gurtner, A., Strano, S., Higashi, Y., Sacchi, A., Piaggio, G., Blandino, G. Mol. Cell. Biol. (2001) [Pubmed]
  7. Independent repressor domains in ZEB regulate muscle and T-cell differentiation. Postigo, A.A., Dean, D.C. Mol. Cell. Biol. (1999) [Pubmed]
  8. Cloning of a cDNA encoding a mouse transcriptional repressor displaying striking sequence conservation across vertebrates. Genetta, T., Kadesch, T. Gene (1996) [Pubmed]
  9. Organization of the gene encoding transcriptional repressor deltaEF1 and cross-species conservation of its domains. Sekido, R., Takagi, T., Okanami, M., Moribe, H., Yamamura, M., Higashi, Y., Kondoh, H. Gene (1996) [Pubmed]
  10. Overlapping positive and negative regulatory elements determine lens-specific activity of the delta 1-crystallin enhancer. Kamachi, Y., Kondoh, H. Mol. Cell. Biol. (1993) [Pubmed]
  11. Zfhx1a and Zfhx1b mRNAs have non-overlapping expression domains during chick and mouse midgestation limb development. Tylzanowski, P., De Valck, D., Maes, V., Peeters, J., Luyten, F.P. Gene Expr. Patterns (2003) [Pubmed]
  12. FOXO transcription factors cooperate with delta EF1 to activate growth suppressive genes in B lymphocytes. Chen, J., Yusuf, I., Andersen, H.M., Fruman, D.A. J. Immunol. (2006) [Pubmed]
  13. Transcriptional activation by the zinc-finger homeodomain protein delta EF1 in estrogen signaling cascades. Dillner, N.B., Sanders, M.M. DNA Cell Biol. (2004) [Pubmed]
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