nfi transcription factors


Summary: Transcription factors that were originally identified as site-specific DNA-binding proteins essential for DNA REPLICATION by ADENOVIRUSES. They play important roles in MAMMARY GLAND function and development.

Top Publications

  1. Gründer A, Ebel T, Mallo M, Schwarzkopf G, Shimizu T, Sippel A, et al. Nuclear factor I-B (Nfib) deficient mice have severe lung hypoplasia. Mech Dev. 2002;112:69-77 pubmed
    ..Our study demonstrates that Nfib is essential for normal lung development, and suggests that it could be involved in the pathogenesis of respiratory distress syndromes in humans. ..
  2. Wang W, Crandall J, Litwack E, Gronostajski R, Kilpatrick D. Targets of the nuclear factor I regulon involved in early and late development of postmitotic cerebellar granule neurons. J Neurosci Res. 2010;88:258-65 pubmed publisher
    ..They also illustrate the importance of NFI as a critical link between cell-intrinsic mechanisms and cell-cell interactions in the development of the mouse cerebellum. ..
  3. Wilczynska K, Singh S, Adams B, Bryan L, Rao R, Valerie K, et al. Nuclear factor I isoforms regulate gene expression during the differentiation of human neural progenitors to astrocytes. Stem Cells. 2009;27:1173-81 pubmed publisher
    ..We conclude that an expression program of NFIs is executed during the differentiation of astrocytes, with NFI-X and -C controlling the expression of astrocytic markers at late stages of differentiation. ..
  4. Roulet E, Busso S, Camargo A, Simpson A, Mermod N, Bucher P. High-throughput SELEX SAGE method for quantitative modeling of transcription-factor binding sites. Nat Biotechnol. 2002;20:831-5 pubmed
    ..A covariance analysis of the selected sites revealed non-independent base preferences at different nucleotide positions, providing insight into the binding mechanism. ..
  5. Park J, Herr Y, Kim H, Gronostajski R, Cho M. Nfic gene disruption inhibits differentiation of odontoblasts responsible for root formation and results in formation of short and abnormal roots in mice. J Periodontol. 2007;78:1795-802 pubmed
    ..This finding suggests that root dentin is required for normal cementum formation. Therefore, Nfic may be a key regulator of root odontoblast differentiation and root formation. ..
  6. Fletcher C, Jenkins N, Copeland N, Chaudhry A, Gronostajski R. Exon structure of the nuclear factor I DNA-binding domain from C. elegans to mammals. Mamm Genome. 1999;10:390-6 pubmed
    ..elegans-like ancestral gene, but that significant changes have occurred in the genomic organization of either the C. elegans or murine NFI genes during evolution. ..
  7. Zhao L, Ba X, Wang X, Zhu X, Wang L, Zeng X. BAF complex is closely related to and interacts with NF1/CTF and RNA polymerase II in gene transcriptional activation. Acta Biochim Biophys Sin (Shanghai). 2005;37:440-6 pubmed
    ..The combined results suggested that BAF complexes can interact with NF1/CTF and RNAP II, and this interaction is closely dependent on the activation of gene transcription. ..
  8. Ferrari S, Simmen K, Dusserre Y, Muller K, Fourel G, Gilson E, et al. Chromatin domain boundaries delimited by a histone-binding protein in yeast. J Biol Chem. 2004;279:55520-30 pubmed
  9. Ling G, Hauer C, Gronostajski R, Pentecost B, Ding X. Transcriptional regulation of rat CYP2A3 by nuclear factor 1: identification of a novel NFI-A isoform, and evidence for tissue-selective interaction of NFI with the CYP2A3 promoter in vivo. J Biol Chem. 2004;279:27888-95 pubmed
    ..These data strongly support a role for NFI transcription factors in the transcriptional activation of CYP2A3.

More Information


  1. Gopalan S, Wilczynska K, Konik B, Bryan L, Kordula T. Nuclear factor-1-X regulates astrocyte-specific expression of the alpha1-antichymotrypsin and glial fibrillary acidic protein genes. J Biol Chem. 2006;281:13126-33 pubmed
    ..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. ..
  2. Gronostajski R. Roles of the NFI/CTF gene family in transcription and development. Gene. 2000;249:31-45 pubmed
    ..Here, we will review the properties of the NFI genes and proteins and their known functions in gene expression and development. ..
  3. Stefancsik R, Sarkar S. Relationship between the DNA binding domains of SMAD and NFI/CTF transcription factors defines a new superfamily of genes. DNA Seq. 2003;14:233-9 pubmed
    ..Based on the structural relationship of their DNA binding domains, we propose that the SMAD and NFI/CTF transcription factors belong to new superfamily of genes. ..
  4. Priolo M, Grosso E, Mammi C, Labate C, Naretto V, Vacalebre C, et al. A peculiar mutation in the DNA-binding/dimerization domain of NFIX causes Sotos-like overgrowth syndrome: a new case. Gene. 2012;511:103-5 pubmed publisher
  5. Campbell C, Piper M, Plachez C, Yeh Y, Baizer J, Osinski J, et al. The transcription factor Nfix is essential for normal brain development. BMC Dev Biol. 2008;8:52 pubmed publisher
    ..The delays seen in eye and ear opening and the brain morphology defects appear independent of the nutritional deprivation, as rescue of perinatal lethality with soft dough does not eliminate these defects. ..
  6. Lee T, Lee D, Kim H, Ko J, Gronostajski R, Cho M, et al. Disruption of Nfic causes dissociation of odontoblasts by interfering with the formation of intercellular junctions and aberrant odontoblast differentiation. J Histochem Cytochem. 2009;57:469-76 pubmed publisher
    ..Collectively, these changes in odontoblasts contributed to development of molars with short and abnormal roots in Nfic-deficient mice...
  7. Piper M, Barry G, Hawkins J, Mason S, Lindwall C, Little E, et al. NFIA controls telencephalic progenitor cell differentiation through repression of the Notch effector Hes1. J Neurosci. 2010;30:9127-39 pubmed publisher
  8. Yoneda Y, Saitsu H, Touyama M, Makita Y, Miyamoto A, Hamada K, et al. Missense mutations in the DNA-binding/dimerization domain of NFIX cause Sotos-like features. J Hum Genet. 2012;57:207-11 pubmed publisher
    ..In individuals with Sotos-like features unrelated to NSD1 changes, genetic testing of NFIX should be considered. ..
  9. Baumeister H, Gronostajski R, Lyons G, Margolis F. Identification of NFI-binding sites and cloning of NFI-cDNAs suggest a regulatory role for NFI transcription factors in olfactory neuron gene expression. Brain Res Mol Brain Res. 1999;72:65-79 pubmed
    ..It now remains to characterize the tissue and cell specific patterns of expression of distinct NFI transcription factors during ontogeny and their roles in regulating gene expression.
  10. Rupp R, Kruse U, Multhaup G, Gobel U, Beyreuther K, Sippel A. Chicken NFI/TGGCA proteins are encoded by at least three independent genes: NFI-A, NFI-B and NFI-C with homologues in mammalian genomes. Nucleic Acids Res. 1990;18:2607-16 pubmed
  11. Cooke D, Lane M. Transcription factor NF1 mediates repression of the GLUT4 promoter by cyclic-AMP. Biochem Biophys Res Commun. 1999;260:600-4 pubmed
  12. Bandyopadhyay S, Starke D, Mieyal J, Gronostajski R. Thioltransferase (glutaredoxin) reactivates the DNA-binding activity of oxidation-inactivated nuclear factor I. J Biol Chem. 1998;273:392-7 pubmed
  13. Wang W, Mullikin Kilpatrick D, Crandall J, Gronostajski R, Litwack E, Kilpatrick D. Nuclear factor I coordinates multiple phases of cerebellar granule cell development via regulation of cell adhesion molecules. J Neurosci. 2007;27:6115-27 pubmed
    ..Furthermore, they reveal how a single transcription factor family can control and integrate multiple aspects of neuronal differentiation through the regulation of cell adhesion molecules. ..
  14. Clark R, Miskimins W, Miskimins R. Cyclic AMP inducibility of the myelin basic protein gene promoter requires the NF1 site. Int J Dev Neurosci. 2002;20:103-11 pubmed
    ..These results demonstrate that the NF1 site is indispensable for cAMP responsiveness of the MBP promoter and, together with other DNA elements, plays a role in controlling MBP gene expression. ..
  15. van Balkom I, Shaw A, Vuijk P, Franssens M, Hoek H, Hennekam R. Development and behaviour in Marshall-Smith syndrome: an exploratory study of cognition, phenotype and autism. J Intellect Disabil Res. 2011;55:973-87 pubmed publisher
  16. Cebolla B, Vallejo M. Nuclear factor-I regulates glial fibrillary acidic protein gene expression in astrocytes differentiated from cortical precursor cells. J Neurochem. 2006;97:1057-70 pubmed
    ..Thus, NFI appears to be an important factor for the integration of astrogenic stimuli in the developing central nervous system. ..
  17. Cooke D, Lane M. The transcription factor nuclear factor I mediates repression of the GLUT4 promoter by insulin. J Biol Chem. 1999;274:12917-24 pubmed
    ..Another as yet unidentified protein, not related to NF1, also binds to the GLUT4 insulin response element and is able to mediate partial repression of the GLUT4 promoter in reporter gene assays. ..
  18. Chaudhry A, Vitullo A, Gronostajski R. Nuclear factor I (NFI) isoforms differentially activate simple versus complex NFI-responsive promoters. J Biol Chem. 1998;273:18538-46 pubmed
    ..Here, we show that NFI heterodimers have intermediate activation potentials compared with homodimers, demonstrating one potential mechanism by which different NFI proteins can regulate gene expression. ..
  19. Roulet E, Armentero M, Krey G, Corthesy B, Dreyer C, Mermod N, et al. Regulation of the DNA-binding and transcriptional activities of Xenopus laevis NFI-X by a novel C-terminal domain. Mol Cell Biol. 1995;15:5552-62 pubmed
    ..Moreover, the region comprising the repressor domain participates in transactivation. Mechanisms that may allow the relief of DNA-binding inhibition in vivo and trigger transcriptional activation are discussed. ..
  20. Bachurski C, Kelly S, Glasser S, Currier T. Nuclear factor I family members regulate the transcription of surfactant protein-C. J Biol Chem. 1997;272:32759-66 pubmed
    ..These data indicate that NFI family member(s), binding to sites in both the promoter and enhancer regions, regulate SP-C gene expression in a process independent of TTF-1. ..
  21. Kumbasar A, Plachez C, Gronostajski R, Richards L, Litwack E. Absence of the transcription factor Nfib delays the formation of the basilar pontine and other mossy fiber nuclei. J Comp Neurol. 2009;513:98-112 pubmed publisher
    ..Collectively, these data demonstrate that Nfib plays an important role in the generation of precerebellar mossy fiber neurons, and may do so at least in part by regulating neurogenesis. ..
  22. Lee D, Park J, Kim H, Ko J, Son H, Gronostajski R, et al. Nuclear factor I-C is essential for odontogenic cell proliferation and odontoblast differentiation during tooth root development. J Biol Chem. 2009;284:17293-303 pubmed publisher
  23. Nilsson J, Helou K, Kovács A, Bendahl P, Bjursell G, Fernö M, et al. Nuclear Janus-activated kinase 2/nuclear factor 1-C2 suppresses tumorigenesis and epithelial-to-mesenchymal transition by repressing Forkhead box F1. Cancer Res. 2010;70:2020-9 pubmed publisher
    ..The relevance of these findings is strengthened by the correlation between FoxF1 expression and a mesenchymal phenoype in breast cancer cell isolates, consistent with the interpretation that FoxF1 promotes invasion and metastasis. ..
  24. Luciakova K, Barath P, Poliakova D, Persson A, Nelson B. Repression of the human adenine nucleotide translocase-2 gene in growth-arrested human diploid cells: the role of nuclear factor-1. J Biol Chem. 2003;278:30624-33 pubmed
    ..Thus, enhanced binding of NF1 is a key step in the growth arrest repression of ANT2 transcription. To our knowledge, this is the first report showing a role for NF1 in growth arrest. ..
  25. Rafty L, Santiago F, Khachigian L. NF1/X represses PDGF A-chain transcription by interacting with Sp1 and antagonizing Sp1 occupancy of the promoter. EMBO J. 2002;21:334-43 pubmed
    ..These findings demonstrate that repression of PDGF-A gene transcription is governed by interplay between NF1/X and Sp1. ..
  26. Plachez C, Lindwall C, Sunn N, Piper M, Moldrich R, Campbell C, et al. Nuclear factor I gene expression in the developing forebrain. J Comp Neurol. 2008;508:385-401 pubmed publisher
    ..Collectively, these data suggest that, in addition to regulating the formation of axon guidance substrates, these genes also have cell-autonomous roles in cortical development. ..
  27. Malan V, Rajan D, Thomas S, Shaw A, Louis Dit Picard H, Layet V, et al. Distinct effects of allelic NFIX mutations on nonsense-mediated mRNA decay engender either a Sotos-like or a Marshall-Smith syndrome. Am J Hum Genet. 2010;87:189-98 pubmed publisher
    ..These findings demonstrate that allelic NFIX mutations trigger distinct phenotypes, depending specifically on their impact on NMD. ..
  28. Fazi F, Rosa A, Fatica A, Gelmetti V, De Marchis M, Nervi C, et al. A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis. Cell. 2005;123:819-31 pubmed
    ..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. ..
  29. Gao B, Jiang L, Kunos G. Transcriptional regulation of alpha(1b) adrenergic receptors (alpha(1b)AR) by nuclear factor 1 (NF1): a decline in the concentration of NF1 correlates with the downregulation of alpha(1b)AR gene expression in regenerating liver. Mol Cell Biol. 1996;16:5997-6008 pubmed
  30. Steele Perkins G, Butz K, Lyons G, Zeichner David M, Kim H, Cho M, et al. Essential role for NFI-C/CTF transcription-replication factor in tooth root development. Mol Cell Biol. 2003;23:1075-84 pubmed
    ..The Nfic mutation is the first mutation described that affects primarily tooth root formation and should greatly aid our understanding of postnatal tooth development. ..
  31. Deneen B, Ho R, Lukaszewicz A, Hochstim C, Gronostajski R, Anderson D. The transcription factor NFIA controls the onset of gliogenesis in the developing spinal cord. Neuron. 2006;52:953-68 pubmed
    ..At later stages, NFIA promotes migration and differentiation of astrocyte precursors, a function that is antagonized in oligodendrocyte precursors by Olig2. ..
  32. Hebbar P, Archer T. Nuclear factor 1 is required for both hormone-dependent chromatin remodeling and transcriptional activation of the mouse mammary tumor virus promoter. Mol Cell Biol. 2003;23:887-98 pubmed
  33. Wong Y, Schulze C, Streichert T, Gronostajski R, Schachner M, Tilling T. Gene expression analysis of nuclear factor I-A deficient mice indicates delayed brain maturation. Genome Biol. 2007;8:R72 pubmed
  34. Tarapore P, Richmond C, Zheng G, Cohen S, Kelder B, Kopchick J, et al. DNA binding and transcriptional activation by the Ski oncoprotein mediated by interaction with NFI. Nucleic Acids Res. 1997;25:3895-903 pubmed
    ..We also find that homodimerization of Ski is essential for co-activation with NFI. However, the C-terminal dimerization domain of c-Ski, which is missing in v-Ski, can be substituted by the leucine zipper domain of GCN4. ..
  35. Inoue T, Tamura T, Furuichi T, Mikoshiba K. Isolation of complementary DNAs encoding a cerebellum-enriched nuclear factor I family that activates transcription from the mouse myelin basic protein promoter. J Biol Chem. 1990;265:19065-70 pubmed
    ..NFI-B proteins translated in vitro could bind to the MBP NFI site. Furthermore, we demonstrated by transfection experiments that NFI-B activated transcription from transfected MBP promoter in neuronal/glial NG108-15 cells. ..
  36. Mason S, Piper M, Gronostajski R, Richards L. Nuclear factor one transcription factors in CNS development. Mol Neurobiol. 2009;39:10-23 pubmed publisher
    ..Here, we discuss the importance and role of NFI in these processes in the context of several CNS systems including the neocortex, hippocampus, cerebellum, and spinal cord at both cellular and molecular levels. ..
  37. Huang X, Xu X, Bringas P, Hung Y, Chai Y. Smad4-Shh-Nfic signaling cascade-mediated epithelial-mesenchymal interaction is crucial in regulating tooth root development. J Bone Miner Res. 2010;25:1167-78 pubmed publisher
    ..The interaction between HERS and the CNC-derived dental mesenchyme may guide the size, shape, and number of tooth roots...
  38. Mitani Y, Li J, Rao P, Zhao Y, Bell D, Lippman S, et al. Comprehensive analysis of the MYB-NFIB gene fusion in salivary adenoid cystic carcinoma: Incidence, variability, and clinicopathologic significance. Clin Cancer Res. 2010;16:4722-31 pubmed publisher
    ..Additional mechanisms may be involved in MYB overexpression in ACCs lacking the MYB-NFIB fusion. These findings suggest that MYB may be a specific novel target for tumor intervention in patients with ACC. ..
  39. Driller K, Pagenstecher A, Uhl M, Omran H, Berlis A, Gründer A, et al. Nuclear factor I X deficiency causes brain malformation and severe skeletal defects. Mol Cell Biol. 2007;27:3855-3867 pubmed
    ..Consistent with the defects in bone ossification we could show that the expression level of tetranectin, a plasminogen-binding protein involved in mineralization, is specifically downregulated in bones of NFIX-deficient mice. ..
  40. Eeckhoute J, Carroll J, Geistlinger T, Torres Arzayus M, Brown M. A cell-type-specific transcriptional network required for estrogen regulation of cyclin D1 and cell cycle progression in breast cancer. Genes Dev. 2006;20:2513-26 pubmed
  41. Chaudhry A, Vitullo A, Gronostajski R. Nuclear factor I-mediated repression of the mouse mammary tumor virus promoter is abrogated by the coactivators p300/CBP and SRC-1. J Biol Chem. 1999;274:7072-81 pubmed
    ..This abrogation of NFI-C-mediated repression by p300/CBP and SRC-1A suggests that repression by NFI-C may occur by interference with coactivator function at the MMTV promoter. ..
  42. Wang W, Stock R, Gronostajski R, Wong Y, Schachner M, Kilpatrick D. A role for nuclear factor I in the intrinsic control of cerebellar granule neuron gene expression. J Biol Chem. 2004;279:53491-7 pubmed
    ..These studies define a new role for NFI proteins as neuronal subtype-enriched transcriptional regulators that participate in an intrinsic transcriptional program directing the differentiation of cerebellar granule neurons. ..
  43. Leahy P, Crawford D, Grossman G, Gronostajski R, Hanson R. CREB binding protein coordinates the function of multiple transcription factors including nuclear factor I to regulate phosphoenolpyruvate carboxykinase (GTP) gene transcription. J Biol Chem. 1999;274:8813-22 pubmed
    ..NFI-A combines with dexamethasone or thyroid hormone in an additive manner to stimulate PEPCK gene transcription. We conclude that CBP coordinates the action of the multiple factors known to control transcription of the PEPCK gene. ..
  44. Murtagh J, Martin F, Gronostajski R. The Nuclear Factor I (NFI) gene family in mammary gland development and function. J Mammary Gland Biol Neoplasia. 2003;8:241-54 pubmed
    ..Here we address the structure and evolution of the NFI gene family and examine the role of the NFI transcription factors in the expression of mammary-gland specific proteins, including whey acidic protein and carboxyl ester ..
  45. Shu T, Butz K, Plachez C, Gronostajski R, Richards L. Abnormal development of forebrain midline glia and commissural projections in Nfia knock-out mice. J Neurosci. 2003;23:203-12 pubmed
    ..2001) appear relatively normal. These results support an essential role for midline glia in callosum development and a role for Nfia in the formation of midline glial structures. ..
  46. das Neves L, Duchala C, Tolentino Silva F, Haxhiu M, Colmenares C, Macklin W, et al. Disruption of the murine nuclear factor I-A gene (Nfia) results in perinatal lethality, hydrocephalus, and agenesis of the corpus callosum. Proc Natl Acad Sci U S A. 1999;96:11946-51 pubmed
    ..This finding of an NFI gene required for a developmental process suggests that the four NFI genes may have distinct roles in vertebrate development. ..
  47. Fujita S, Ito T, Mizutani T, Minoguchi S, Yamamichi N, Sakurai K, et al. miR-21 Gene expression triggered by AP-1 is sustained through a double-negative feedback mechanism. J Mol Biol. 2008;378:492-504 pubmed publisher
    ..Since exogenous miR-21 expression moderately induced endogenous miR-21, an evolutionarily conserved double-negative feedback regulation would be operating as a mechanism to sustain miR-21 expression. ..
  48. Nilsson J, Bjursell G, Kannius Janson M. Nuclear Jak2 and transcription factor NF1-C2: a novel mechanism of prolactin signaling in mammary epithelial cells. Mol Cell Biol. 2006;26:5663-74 pubmed
    ..Hence, we describe a novel pathway through which nuclear Jak2 is subject to regulation by prolactin in mammary epithelial cells. ..
  49. Bandyopadhyay S, Gronostajski R. Identification of a conserved oxidation-sensitive cysteine residue in the NFI family of DNA-binding proteins. J Biol Chem. 1994;269:29949-55 pubmed
    ..The presence of this nonessential Cys-3 residue in all known NFI proteins raises the possibility that it may function in a manner similar to redox-sensitive cysteine residues found in other site-specific DNA-binding proteins. ..
  50. Qian F, Kruse U, Lichter P, Sippel A. Chromosomal localization of the four genes (NFIA, B, C, and X) for the human transcription factor nuclear factor I by FISH. Genomics. 1995;28:66-73 pubmed
    ..3 in the order centromere-NFIX-NFIC-telomere. Comparison of the position of NFI genes and JUN genes revealed a close physical linkage between members of the NFI and JUN gene families in the human genome. ..
  51. Wickenheisser J, Nelson Degrave V, Quinn P, McAllister J. Increased cytochrome P450 17alpha-hydroxylase promoter function in theca cells isolated from patients with polycystic ovary syndrome involves nuclear factor-1. Mol Endocrinol. 2004;18:588-605 pubmed
  52. Johansson E, Kannius Janson M, Bjursell G, Nilsson J. The p53 tumor suppressor gene is regulated in vivo by nuclear factor 1-C2 in the mouse mammary gland during pregnancy. Oncogene. 2003;22:6061-70 pubmed
    ..It is also the first time that p53 gene activation is coupled to a specific, endogenously expressed NF1 isoform. ..
  53. Kane R, Murtagh J, Finlay D, Marti A, Jaggi R, Blatchford D, et al. Transcription factor NFIC undergoes N-glycosylation during early mammary gland involution. J Biol Chem. 2002;277:25893-903 pubmed