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Gene Review

NFIA  -  nuclear factor I/A

Homo sapiens

Synonyms: CCAAT-box-binding transcription factor, CTF, KIAA1439, NF-I/A, NF1-A, ...
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Disease relevance of NFIA

  • In line with this, both RNAi against NFI-A and ectopic expression of miR-223 in acute promyelocytic leukemia (APL) cells enhance differentiation, whereas miR-223 knockdown inhibits the differentiation response to RA [1].
  • The hypergastrinemic patients (MEN-1, pernicious anemia) had elevated plasma Gamide but unaltered CTFP demonstrating differential secretion of these 2 progastrin-derived peptides [2].
  • The objectives were to determine the concentration of CTFP in normal subjects and patients with gastrointestinal diseases and to investigate the biological activity of CTFP [2].
  • 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 [3].
  • The TGGCA-binding protein from HeLa cells appears to be identical to nuclear factor I described by others, which stimulates initiation of adenovirus DNA replication in vitro [4].

High impact information on NFIA

  • A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis [1].
  • Altogether, our data indicate that miR-223 plays a crucial role during granulopoiesis and point to the NFI-A repression as an important molecular pathway mediating gene reprogramming in this cell lineage [1].
  • The two factors compete for binding to the miR-223 promoter: NFI-A maintains miR-223 at low levels, whereas its replacement by C/EBPalpha, following retinoic acid (RA)-induced differentiation, upregulates miR-223 expression [1].
  • However, Notch effectors are unable to promote glial-fate specification in the absence of NFIA [5].
  • At later stages, NFIA promotes migration and differentiation of astrocyte precursors, a function that is antagonized in oligodendrocyte precursors by Olig2 [5].

Biological context of NFIA

  • A significant relationship was found between 24-h SBP, 24-h heart rate, and pulse wave velocity in healthy subjects, but not in all NF1 patients and also between the NF1A and NF1B groups [6].
  • 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 [7].
  • To determine whether SP-C expression is regulated by NFI in vivo, a chimeric fusion protein containing the DNA binding and dimerization domain of NFI-A and the Drosophila engrailed transcriptional repression domain (NFIen) was conditionally expressed in mice under control of a doxycycline-inducible transgene [8].
  • Site-specific mutation of the proximal or distal NFI sites drastically reduced transactivation by a co-transfected NFI-A expression vector in HeLa cells [9].
  • Since DAPT treatment resulted in increased beta2-CTF levels, we also tested whether beta2-CTFs or beta2-ICDs would directly affect cell migration by overexpressing recombinant proteins [10].

Anatomical context of NFIA


Associations of NFIA with chemical compounds

  • We have previously purified NF1-A and NF1-B from rat liver as factors that bind to the silencer in the glutathione transferase P gene, and have also reported the repression domain of NF1-A [12].
  • NFI-A combines with dexamethasone or thyroid hormone in an additive manner to stimulate PEPCK gene transcription [13].
  • PS1 and PS2 are polytopic membrane proteins that undergo endoproteolytic cleavage to generate stable NH2- and COOH-terminal derivatives (NTF and CTF, respectively) [3].
  • Whereas some repression domains identified previously are enriched with alanine, proline, or serine, and are associated with the general transcription factors, the NF1-A repression domains did not interact with transcription factor IIB, TATA-binding protein (TBP), or TBP-associated factors in vitro [14].
  • We show that aspartate-mutant holoprotein presenilins are not incorporated into the high molecular weight, NTF/CTF-containing complexes [15].

Other interactions of NFIA

  • We have previously isolated several splicing variant cDNAs derived from four NF1 genes of rat, and elucidated the structure of the rat Nfia gene [16].

Analytical, diagnostic and therapeutic context of NFIA

  • EXPERIMENTAL DESIGN: Polymeric microspheres made of poly(lactic-co-glycolic acid) (PLGA) were loaded with very low amounts of PEX and PF-4/CTF [11].
  • 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 [11].
  • The insertion of a chest tube was required in only one (2%) procedure using the CTF technique, while this was needed in four (10%) using the conventional technique [17].


  1. A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis. Fazi, F., Rosa, A., Fatica, A., Gelmetti, V., De Marchis, M.L., Nervi, C., Bozzoni, I. Cell (2005) [Pubmed]
  2. Production, secretion, and biological activity of the C-terminal flanking Peptide of human progastrin. Smith, K.A., Patel, O., Lachal, S., Jennings, I., Kemp, B., Burgess, J., Baldwin, G.S., Shulkes, A. Gastroenterology (2006) [Pubmed]
  3. 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]
  4. 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]
  5. The Transcription Factor NFIA Controls the Onset of Gliogenesis in the Developing Spinal Cord. Deneen, B., Ho, R., Lukaszewicz, A., Hochstim, C.J., Gronostajski, R.M., Anderson, D.J. Neuron (2006) [Pubmed]
  6. Arterial distensibility and ambulatory blood pressure monitoring in young patients with neurofibromatosis type 1. Tedesco, M.A., Di Salvo, G., Ratti, G., Natale, F., Calabrese, E., Grassia, C., Iacono, A., Lama, G. Am. J. Hypertens. (2001) [Pubmed]
  7. Roles of the NFI/CTF gene family in transcription and development. Gronostajski, R.M. Gene (2000) [Pubmed]
  8. Nuclear factor I/thyroid transcription factor 1 interactions modulate surfactant protein C transcription. Bachurski, C.J., Yang, G.H., Currier, T.A., Gronostajski, R.M., Hong, D. Mol. Cell. Biol. (2003) [Pubmed]
  9. Nuclear factor I family members regulate the transcription of surfactant protein-C. Bachurski, C.J., Kelly, S.E., Glasser, S.W., Currier, T.A. J. Biol. Chem. (1997) [Pubmed]
  10. Presenilin/gamma-secretase-mediated cleavage of the voltage-gated sodium channel beta2-subunit regulates cell adhesion and migration. Kim, D.Y., Ingano, L.A., Carey, B.W., Pettingell, W.H., Kovacs, D.M. J. Biol. Chem. (2005) [Pubmed]
  11. 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]
  12. Expression, DNA-binding specificity and transcriptional regulation of nuclear factor 1 family proteins from rat. Osada, S., Matsubara, T., Daimon, S., Terazu, Y., Xu, M., Nishihara, T., Imagawa, M. Biochem. J. (1999) [Pubmed]
  13. CREB binding protein coordinates the function of multiple transcription factors including nuclear factor I to regulate phosphoenolpyruvate carboxykinase (GTP) gene transcription. Leahy, P., Crawford, D.R., Grossman, G., Gronostajski, R.M., Hanson, R.W. J. Biol. Chem. (1999) [Pubmed]
  14. Identification of the transcriptional repression domain of nuclear factor 1-A. Osada, S., Ikeda, T., Xu, M., Nishihara, T., Imagawa, M. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  15. 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]
  16. Organization of gene structure and expression of nuclear factor 1 family in rat. Osada, S., Imagawa, M., Nishihara, T. DNA Seq. (2005) [Pubmed]
  17. 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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