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Gene Review

ZIC1  -  Zic family member 1

Homo sapiens

Synonyms: ZIC, ZNF201, Zinc finger protein 201, Zinc finger protein ZIC 1, Zinc finger protein of the cerebellum 1
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Disease relevance of ZIC1


High impact information on ZIC1

  • We have identified the zinc-finger transcription factor Zic1 as a regulator of Math1 expression [5].
  • Ten cDNA clones that encoded portions of the human Zic1 (five clones) and Zic2 (five clones) transcription factors were isolated [3].
  • We first established an optimal binding sequence for Zic1, Zic2, and Zic3 proteins by electrophoretic mobility shift assay-based target selection and mutational analysis [6].
  • Multiple consensus binding sites for specific transcription factor families within the BIRM are required for its activity and some of these regions are phylogenetically conserved between orthologous vertebrate zic1 genes [7].
  • Previous work identified four related elements (ZIA, ZIB, ZIC, and ZID) and a cyclic AMP response element binding-AP-1 element (ZII) that are involved in the induction of the BZLF1 promoter (Zp) by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (E. Flemington and S. H. Speck, J. Virol. 64:1217-1226, 1990) [8].

Biological context of ZIC1


Anatomical context of ZIC1

  • While Zic1 does not act as a neural inducer, it synergizes with the neural inducing factor Noggin to activate expression of posterior neural genes, including the midbrain/hindbrain boundary marker engrailed-2 [11].
  • Here Sp1 and Sp3 are identified as the cellular factors present in crude B cell nuclear extract preparations that bind to the ZIC domain [12].

Other interactions of ZIC1

  • Our data indicate that ZIC1, ZIC2, and ZIC3 are not major risk factors for NTD in humans [13].
  • The sequence of the zinc finger domain exhibits highest homology with those of members of the GLI and ZIC subfamilies of Krüppel-like proteins [14].
  • Cerebellar vermis aplasia: patient report and exclusion of the candidate genes EN2 and ZIC1 [15].


  1. Heterozygous deletion of the linked genes ZIC1 and ZIC4 is involved in Dandy-Walker malformation. Grinberg, I., Northrup, H., Ardinger, H., Prasad, C., Dobyns, W.B., Millen, K.J. Nat. Genet. (2004) [Pubmed]
  2. Genes differentially expressed in medulloblastoma and fetal brain. Michiels, E.M., Oussoren, E., Van Groenigen, M., Pauws, E., Bossuyt, P.M., Voûte, P.A., Baas, F. Physiol. Genomics (1999) [Pubmed]
  3. Transcription factors Zic1 and Zic2 bind and transactivate the apolipoprotein E gene promoter. Salero, E., Pérez-Sen, R., Aruga, J., Giménez, C., Zafra, F. J. Biol. Chem. (2001) [Pubmed]
  4. Cerebellar degeneration and autoimmunity to zinc-finger proteins of the cerebellum. Bataller, L., Wade, D.F., Fuller, G.N., Rosenfeld, M.R., Dalmau, J. Neurology (2002) [Pubmed]
  5. Zic1 represses Math1 expression via interactions with the Math1 enhancer and modulation of Math1 autoregulation. Ebert, P.J., Timmer, J.R., Nakada, Y., Helms, A.W., Parab, P.B., Liu, Y., Hunsaker, T.L., Johnson, J.E. Development (2003) [Pubmed]
  6. Molecular properties of Zic proteins as transcriptional regulators and their relationship to GLI proteins. Mizugishi, K., Aruga, J., Nakata, K., Mikoshiba, K. J. Biol. Chem. (2001) [Pubmed]
  7. Identification of a BMP inhibitor-responsive promoter module required for expression of the early neural gene zic1. Tropepe, V., Li, S., Dickinson, A., Gamse, J.T., Sive, H.L. Dev. Biol. (2006) [Pubmed]
  8. Characterization of the ZI domains in the Epstein-Barr virus BZLF1 gene promoter: role in phorbol ester induction. Borras, A.M., Strominger, J.L., Speck, S.H. J. Virol. (1996) [Pubmed]
  9. Joubert syndrome: a haplotype segregation strategy and exclusion of the zinc finger protein of cerebellum 1 (ZIC1) gene. Bennett, C.L., Parisi, M.A., Eckert, M.L., Huynh, H.M., Chance, P.F., Glass, I.A. Am. J. Med. Genet. A (2004) [Pubmed]
  10. Investigation of downstream target genes of PAX3c, PAX3e and PAX3g isoforms in melanocytes by microarray analysis. Wang, Q., Kumar, S., Mitsios, N., Slevin, M., Kumar, P. Int. J. Cancer (2007) [Pubmed]
  11. The zic1 gene is an activator of Wnt signaling. Merzdorf, C.S., Sive, H.L. Int. J. Dev. Biol. (2006) [Pubmed]
  12. Binding of the ubiquitous cellular transcription factors Sp1 and Sp3 to the ZI domains in the Epstein-Barr virus lytic switch BZLF1 gene promoter. Liu, S., Borras, A.M., Liu, P., Suske, G., Speck, S.H. Virology (1997) [Pubmed]
  13. Genetic variants in ZIC1, ZIC2, and ZIC3 are not major risk factors for neural tube defects in humans. Klootwijk, R., Groenen, P., Schijvenaars, M., Hol, F., Hamel, B., Straatman, H., Steegers-Theunissen, R., Mariman, E., Franke, B. Am. J. Med. Genet. A (2004) [Pubmed]
  14. Genomic structure of the gene encoding the human GLI-related, Krüppel-like zinc finger protein GLIS2. Zhang, F., Jetten, A.M. Gene (2001) [Pubmed]
  15. Cerebellar vermis aplasia: patient report and exclusion of the candidate genes EN2 and ZIC1. Titomanlio, L., Pierri, N.B., Romano, A., Imperati, F., Borrelli, M., Barletta, V., Diano, A.A., Castaldo, I., Santoro, L., Del Giudice, E. Am. J. Med. Genet. A (2005) [Pubmed]
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