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Gene Review

NFIX  -  nuclear factor I/X (CCAAT-binding...

Homo sapiens

Synonyms: CCAAT-box-binding transcription factor, CTF, MRSHSS, NF-I/X, NF1-X, ...
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Disease relevance of NFIX

  • Binding sites for CTF in the human Ha-ras and alpha-globin promoters were highly homologous to sequences recognized by nuclear factor I (NF-I), a cellular DNA-binding protein that is required for the initiation of adenovirus DNA replication in vitro [1].
  • A mammary cell-specific enhancer in mouse mammary tumor virus DNA is composed of multiple regulatory elements including binding sites for CTF/NFI and a novel transcription factor, mammary cell-activating factor [2].
  • JC virus susceptibility correlated with significantly higher expression of the NFI-X transcription factor in astrocytes than in neurons [3].
  • In the present report, we examine the disposition of PS NTF and CTF assemblies in stable mouse N2a neuroblastoma cell lines expressing human PS polypeptides [4].
  • A single local s.c. injection of PLGA microspheres loaded with low amounts of PEX or PF-4/CTF resulted in an 88% and 95% reduction in glioma tumor volume 30 days post-treatment [5].

High impact information on NFIX

  • We studied a model viral chromosome containing a single binding site for the cellular transcriptional activator, nuclear factor I (NF-I/CTF), located adjacent to the replication origin [6].
  • CTF and NF-I were found to be indistinguishable in polypeptide composition, DNA-binding properties, immunological cross-reactivity, and in vitro stimulation of DNA replication and transcription initiation [1].
  • Together, these two domains constitute the full NFI-X transactivation potential [7].
  • Furthermore, transfection of an NFI-X expression vector into progenitor-derived neuronal cells before infection resulted in viral protein production [3].
  • In addition, we found, using isoform-specific siRNAs, that NFI-X regulates the astrocyte-specific expression of ACT and GFAP [8].

Biological context of NFIX

  • This property, combined with the differential expression of NFI-X, can achieve cell-type specificity of NFI dependent promoters and enhancers [9].
  • Cloning and functional analysis of spliced isoforms of human nuclear factor I-X: interference with transcriptional activation by NFI/CTF in a cell-type specific manner [9].
  • The activity of the nuclear factor I/CCAAT transcription factor (NFI/CTF) is negatively regulated by oxidative stress [10].
  • In this study, we determined the genomic organization and nucleotide sequences of the exon/intron boundaries of the rat Nfib, Nfic and Nfix genes in silico [11].
  • The adenovirus origin of DNA replication is located within the terminal 51 bp of the viral genome and contains three recognizable domains: the minimal origin or "core" and binding sites for the cellular transcription factors NFI (CTF) and NFIII (oct-1, OTF-I) [12].

Anatomical context of NFIX


Associations of NFIX with chemical compounds

  • The addition of relatively high (millimolar) H(2)O(2) concentrations inactivates cellular NFI DNA-binding activity whereas lower concentrations can repress NFI/CTF transactivating function [10].
  • The Nuclear Factor I (NFI) family of site-specific DNA-binding proteins (also known as CTF or CAAT box transcription factor) functions both in viral DNA replication and in the regulation of gene expression [15].
  • PS1 and PS2 are polytopic membrane proteins that undergo endoproteolytic cleavage to generate stable NH2- and COOH-terminal derivatives (NTF and CTF, respectively) [4].
  • We show that aspartate-mutant holoprotein presenilins are not incorporated into the high molecular weight, NTF/CTF-containing complexes [16].

Other interactions of NFIX

  • We propose that NFI-X cooperates with AP-1 by an unknown mechanism in astrocytes, which results in the expression of a subset of astrocyte-specific genes [8].

Analytical, diagnostic and therapeutic context of NFIX


  1. A cellular DNA-binding protein that activates eukaryotic transcription and DNA replication. Jones, K.A., Kadonaga, J.T., Rosenfeld, P.J., Kelly, T.J., Tjian, R. Cell (1987) [Pubmed]
  2. A mammary cell-specific enhancer in mouse mammary tumor virus DNA is composed of multiple regulatory elements including binding sites for CTF/NFI and a novel transcription factor, mammary cell-activating factor. Mink, S., Härtig, E., Jennewein, P., Doppler, W., Cato, A.C. Mol. Cell. Biol. (1992) [Pubmed]
  3. Lineage pathway of human brain progenitor cells identified by JC virus susceptibility. Messam, C.A., Hou, J., Gronostajski, R.M., Major, E.O. Ann. Neurol. (2003) [Pubmed]
  4. Evidence that intramolecular associations between presenilin domains are obligatory for endoproteolytic processing. Saura, C.A., Tomita, T., Davenport, F., Harris, C.L., Iwatsubo, T., Thinakaran, G. J. Biol. Chem. (1999) [Pubmed]
  5. Continuous delivery of endogenous inhibitors from poly(lactic-co-glycolic acid) polymeric microspheres inhibits glioma tumor growth. Benny, O., Duvshani-Eshet, M., Cargioli, T., Bello, L., Bikfalvi, A., Carroll, R.S., Machluf, M. Clin. Cancer Res. (2005) [Pubmed]
  6. Transcriptional activator nuclear factor I stimulates the replication of SV40 minichromosomes in vivo and in vitro. Cheng, L., Kelly, T.J. Cell (1989) [Pubmed]
  7. Regulation of the DNA-binding and transcriptional activities of Xenopus laevis NFI-X by a novel C-terminal domain. Roulet, E., Armentero, M.T., Krey, G., Corthésy, B., Dreyer, C., Mermod, N., Wahli, W. Mol. Cell. Biol. (1995) [Pubmed]
  8. Nuclear Factor-1-X Regulates Astrocyte-specific Expression of the {alpha}1-Antichymotrypsin and Glial Fibrillary Acidic Protein Genes. Gopalan, S.M., Wilczynska, K.M., Konik, B.S., Bryan, L., Kordula, T. J. Biol. Chem. (2006) [Pubmed]
  9. Cloning and functional analysis of spliced isoforms of human nuclear factor I-X: interference with transcriptional activation by NFI/CTF in a cell-type specific manner. Apt, D., Liu, Y., Bernard, H.U. Nucleic Acids Res. (1994) [Pubmed]
  10. The repression of nuclear factor I/CCAAT transcription factor (NFI/CTF) transactivating domain by oxidative stress is mediated by a critical cysteine (Cys-427). Morel, Y., Barouki, R. Biochem. J. (2000) [Pubmed]
  11. Organization of gene structure and expression of nuclear factor 1 family in rat. Osada, S., Imagawa, M., Nishihara, T. DNA Seq. (2005) [Pubmed]
  12. Interactions between the adenovirus type 2 DNA polymerase and the DNA binding domain of nuclear factor I. Bosher, J., Robinson, E.C., Hay, R.T. New Biol. (1990) [Pubmed]
  13. Promoter region of the human gene coding for beta-chain of C4b binding protein. Hepatocyte nuclear factor-3 and nuclear factor-I/CTF transcription factors are required for efficient expression of C4BPB in HepG2 cells. Arenzana, N., Rodríguez de Córdoba, S. J. Immunol. (1996) [Pubmed]
  14. The TGGCA protein binds to the MMTV-LTR, the adenovirus origin of replication, and the BK virus enhancer. Nowock, J., Borgmeyer, U., Püschel, A.W., Rupp, R.A., Sippel, A.E. Nucleic Acids Res. (1985) [Pubmed]
  15. Roles of the NFI/CTF gene family in transcription and development. Gronostajski, R.M. Gene (2000) [Pubmed]
  16. Mutation of conserved aspartates affect maturation of presenilin 1 and presenilin 2 complexes. Yu, G., Chen, F., Nishimura, M., Steiner, H., Tandon, A., Kawarai, T., Arawaka, S., Supala, A., Song, Y.Q., Rogaeva, E., Holmes, E., Zhang, D.M., Milman, P., Fraser, P., Haass, C., St George-Hyslop, P. Acta Neurol. Scand., Suppl. (2000) [Pubmed]
  17. Regulation of renin enhancer activity by nuclear factor I and Sp1/Sp3. Pan, L., Glenn, S.T., Jones, C.A., Gronostajski, R.M., Gross, K.W. Biochim. Biophys. Acta (2003) [Pubmed]
  18. Accuracy and complications in computed tomography fluoroscopy-guided needle biopsies of lung masses. Heck, S.L., Blom, P., Berstad, A. European radiology. (2006) [Pubmed]
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