mnC1 homozygote and WT worm
The Gronostajski Lab:
The Nuclear Factor I (NFI) family of transcription/replication proteins

  • Role of NFI proteins in mammalian and nematode development. 
  • Mechanisms of transcriptional modulation by NFI proteins. 
  • Structure and Function of NFI DNA-binding domain.
  • Link to NFI expression vector page.
  • Quicktime movie of worm development
  •      Requires Quicktime: 4-cell to adult (size 2Mb)
  • In vivo target gene selectivity of T-box transcription factors
  • New!  Link to NFI-Regulome Database.
  • Real-time PCR primers for mouse NFI genes.
  • Brief Description:

    The goal of our laboratory is to gain a better understanding of how proteins that interact with DNA regulate RNA transcription, DNA replication and metazoan development.  Our focus is on the structure and function of the Nuclear Factor I (NFI) family of site-specific DNA binding proteins.  In vertebrates, NFI family members function in both the replication of viral DNA and the transcription of viral and cellular genes.  We are currently analyzing the role of the NFI gene family in both vertebrate and C. elegans development. Studies on mouse NFI genes can be divided into two major themes: (1) biochemical analysis of NFI protein structure and function and (2) molecular genetic studies on NFI's role in cell growth, differentiation and development.  We are also assessing the function of the single C. elegans NFI gene (nfi-1, (3)) and have constructed and are annotating the NFI-Regulome database which contains all genes for which there is published evidence for regulation by NFI transcription factors (4).

    (1) The DNA-binding domain of NFI differs from those found in other well characterized DNA-binding proteins. Four major questions being addressed in the laboratory are: What is the structure of the NFI DNA-binding domain? How does NFI recognize and interact with DNA? Does NFI change the structure of DNA when it binds? What proteins interact with NFI to stimulate RNA transcription and/or DNA replication?  We are asking these questions both in our laboratory and in collaboration with a number of talented investigators.

    We have shown that the NFI-C protein represses the glucocorticoid-dependent expression of the MMTV promoter.  This repression can be overcome by overexpression of the co-activator proteins CBP, p300 or SRC-1, suggesting a role of these co-activators in MMTV expression.  Surprisingly, NFI-C doesn't repress progesterone stimulation of MMTV.  We are currently working out the biochemical mechanism for this repression by NFI-C and the roles of co-activators, histone acetylase activity and chromatin remodeling activity in the process.

    (2) We've been generating targeted mutations in mouse NFI genes to determine the roles of the different NFI family members in development.

    The NFI-A deficient mouse we generated (Nfia-) has major neurological defects including agenesis of the corpus callosum, hydrocephalus and defects, in the generation of specific midline glial cell populations.  We're now studying the biochemical pathways leading to these developmental defects with the goal of determining how loss of a single transcription factor results in major neuroanatomical changes.  We're focusing on whether loss of NFI-A causes changes in: 1) cell proliferation or death, 2) cell migration or differentiation, 3) axonal outgrowth, 4) axonal pathfinding, 5) glial cell differentiation and 6) patterns of neuronal or glial cell gene expression.

    The NFI-C deficient mouse we generated (Nfic-) has novel defects in tooth development.  Although NFI-C was one of the first transcription factors cloned and is expressed in many embryonic and adult tissues, the only defect seen in mice lacking Nfic is that the molar roots fail to develop and the incisors are dysmorphic and poorly developed.  This defect is severe enough that most mutant mice die within a few months if fed a standard lab chow, but have a normal lifespan and are fertile if fed a soft dough diet.  Since this is the first mutation that affects primarily tooth root formation, it should allow us to determine the molecular pathways needed for this important postnatal developmental process.

    The NFI-B deficient mouse we recently made (Nfib-) has both major neuroanatomical defects and defects in lung maturation.  The brain defects are more extensive then seen in the Nfia- mouse above and include agenesis of the corpus callosum, loss of the basilar pons, and hippocampal defects.  The lung defects are of interest since lung immaturity is a major problem in premature newborns.  We are determining the biochemical and genetic pathways by which Nfib regulates lung maturation.  We're also determining the specific cell type in the lung in which Nfib is required for normal lung maturation.

    Most recently, the NFI-X knockout mouse we've made (Nfix-) has an ENLARGED brain and abnormal cells that contain markers of neural stem cells within the normally empty cerebral ventricles.  We're characterizing these cells and how they relate to the increased brain size.  We've also shown that NFI-X functions in both the switch between quiescence and activation of adult neural stem cells and in the decision made by neural stem cells to proceed down the neural, astrocyte and oligodendrocyte lineages.  Since we've also shown that NFI-A and NFI-B affect lineage determination we are examining the interaction of these 3 genes in neural stem cell homeostasis.

    (3) While all vertebrates examined contain 4 highly conserved NFI genes (NFI-A, -B, -C and -X), the nematode Caenorhabditis elegans has only a single NFI gene (nfi-1). Unlike the case in vertebrates, where all 4 NFI genes are expressed in many tissues during both embryogenesis and throughout adult life, the C. elegans nfi-1 gene is expressed primarily during embryogenesis.  We've shown that worms lacking nfi-1 are viable, but have several interesting phenotypes including a shortened lifespan.  We've demonstrated the first cell-autonomous function of NFI by showing that expression of the protein specifically in pharyngeal muscle cells rescues the pharyngeal pumping defect and shortened lifespan of nfi-1 deficient animals.  We're also published the mapping the in vivo binding sites of NFI-1 in whole worms, the first whole genome analysis of in vivo NFI binding sites in any organism.

    (4) We have created the NFI-Regulome database, which contains all genes for which there is published evidence that NFI transcription factors regulate their expression.  This database is a work in progress with several dozens of genes being annotated with a few hundred to go.  We will soon be able to query this database for tissue- and cell-type specific genes regulated by known transcription factors that cooperate with NFI proteins.

    Picture of NFI-C in mouse molar
    Above is a picture of NFI expression in the developing mouse embryo. These in situs were produced through a collaboration with Dr. Gary Lyons. For a closer look click here!(800kB,beware) NFI-C expression in P15 mouse molar.  Note expression in Odontoblasts and Preodontoblasts.  Picture is courtesy of ASM and appears as the cover of the April, 2003 Mol. Cell Biol.
    Pictures of WT and nfi-1 null worms
    Above are images of Wild Type (A-C) and nfi-1 null C. elegans (D-F).   Single young adults were spotted in the center of fresh plates and left for 10 min. (A, D) Photographs of N2 worms and nfi-1 mutants; (B, E) Track patterns of N2 worms and nfi-1 mutants; (C, F) Track patterns of N2 worms and nfi-1 mutants with higher magnification. Note less regular tracks in nfi-1 mutant vs. N2 worms.
    A Nuclear Factor I binding Site on DNA

    For those structurally minded people, here's a molecular model of an NFI binding site (TTGGCNNNNNGCCAA is the consensus sequence on duplex DNA). The green balls represent nitrogens in methyl groups of thymidine residues in the major groove while the red balls represent nitrogens in guanosine residues in the major groove protected from methylation by NFI. We don't know what the protein looks like sitting on DNA, but we're working on it!

    Expression of an nfi-1-lacZ transgene

         Above are pictures of C. elegans embryos expressing an nfi-1-lacZ transgene.  Expression occurs only during embryogenesis and not in the adult worm.  Expression starts in a few cells and appears to spread throughout most of the embryo.  We are currently identifying the cell types in which nfi-1 is expressed. 

    Members of the Lab:

    Selected Lab References:
    (Click on those with links for PDF file download)

    Grabowska, M. M., S. M. Kelly, A. L. Reese, J. M. Cates, T. C. Case, J. Zhang, D. J. DeGraff, D. W. Strand, N. L. Miller, P. E. Clark, S. W. Hayward, R. M. Gronostajski, P. D. Anderson, and R. J. Matusik. Nfib Regulates Transcriptional Networks That Control the Development of Prostatic Hyperplasia. Endocrinol. 157 (2016) 1094-109. PMID:26677878 PMC:PMC4769366

    Ding, B., J. W. Cave, P. R. Dobner, D. Mullikin-Kilpatrick, M. Bartzokis, H. Zhu, C. W. Chow, R. M. Gronostajski, and D. L. Kilpatrick. Reciprocal autoregulation by NFI occupancy and ETV1 promotes the developmental expression of dendrite-synapse genes in cerebellar granule neurons. Mol. Biol. Cell 27 (2016) 1488-99. PMID:26941328 PMC:PMC4850036

    Zhou, B., J. M. Osinski, J. L. Mateo, B. Martynoga, F. J. Sim, C. E. Campbell, F. Guillemot, M. Piper, and R. M. Gronostajski. Loss of NFIX Transcription Factor Biases Postnatal Neural Stem/Progenitor Cells Toward Oligodendrogenesis. Stem Cells Dev 24 (2015) 2114-26. PMID:26083238

    Vidovic, D., L. Harris, T. J. Harvey, Y. H. Evelyn Heng, A. G. Smith, J. Osinski, J. Hughes, P. Thomas, R. M. Gronostajski, T. L. Bailey, and M. Piper. Expansion of the lateral ventricles and ependymal deficits underlie the hydrocephalus evident in mice lacking the transcription factor NFIX. Brain Res. 1616 (2015) 71-87. PMID:25960350

    O'Connor, C., J. Campos, J. M. Osinski, R. M. Gronostajski, A. M. Michie, and K. Keeshan. Nfix expression critically modulates early B lymphopoiesis and myelopoiesis. PLoS One 10 (2015) e0120102. PMID:25780920 PMC:4363787

    Mellas, R. E., H. Kim, J. Osinski, S. Sadibasic, R. M. Gronostajski, M. Cho, and O. J. Baker. NFIB Regulates Embryonic Development of Submandibular Glands. J. Dent. Res. 94 (2015) 312-9. PMID:25403566

    Heng, Y. H., B. Zhou, L. Harris, T. Harvey, A. Smith, E. Horne, B. Martynoga, J. Andersen, A. Achimastou, K. Cato, L. J. Richards, R. M. Gronostajski, G. S. Yeo, F. Guillemot, T. L. Bailey, and M. Piper. NFIX Regulates Proliferation and Migration Within the Murine SVZ Neurogenic Niche. Cereb. Cortex 25 (2015) 3758-78. PMID:25331604 PMC:PMC4585514

    Harris, L., L. A. Genovesi, R. M. Gronostajski, B. J. Wainwright, and M. Piper. Nuclear factor one transcription factors: Divergent functions in developmental versus adult stem cell populations. Dev Dyn 244 (2015) 227-38. PMID:25156673

    Grabowska, M. M., S. M. Kelly, A. L. Reese, J. M. Cates, T. C. Case, J. Zhang, D. J. DeGraff, D. W. Strand, N. L. Miller, P. E. Clark, S. W. Hayward, R. M. Gronostajski, P. D. Anderson, and R. J. Matusik. Nfib regulates transcriptional networks that control the development of prostatic hyperplasia. Endocrinol. (2015) en20151312. PMID:26677878

    Robinson, G. W., K. Kang, K. H. Yoo, Y. Tang, B. M. Zhu, D. Yamaji, V. Colditz, S. J. Jang, R. M. Gronostajski, and L. Hennighausen. Coregulation of Genetic Programs by the Transcription Factors NFIB and STAT5. Mol. Endocrinol. 28 (2014) 758-67. PMID:24678731 PMC:4004779

    Piper, M., G. Barry, T. J. Harvey, R. McLeay, A. G. Smith, L. Harris, S. Mason, B. W. Stringer, B. W. Day, N. R. Wray, R. M. Gronostajski, T. L. Bailey, A. W. Boyd, and L. J. Richards. NFIB-Mediated Repression of the Epigenetic Factor Ezh2 Regulates Cortical Development. J. Neurosci. 34 (2014) 2921-30. PMID:24553933

    Lee, D. S., H. W. Choung, H. J. Kim, R. M. Gronostajski, Y. I. Yang, H. M. Ryoo, Z. H. Lee, H. H. Kim, E. S. Cho, and J. C. Park. NFI-C Regulates Osteoblast Differentiation via Control of Osterix Expression. Stem Cells 32 (2014) 2467-79. PMID:24801901

    Lajoie, M., Y. C. Hsu, R. M. Gronostajski, and T. L. Bailey. An overlapping set of genes is regulated by both NFIB and the glucocorticoid receptor during lung maturation. BMC genomics 15 (2014) 231. PMID:24661679 PMC:4023408

    Heng, Y. H., R. C. McLeay, T. J. Harvey, A. G. Smith, G. Barry, K. Cato, C. Plachez, E. Little, S. Mason, C. Dixon, R. M. Gronostajski, T. L. Bailey, L. J. Richards, and M. Piper. NFIX regulates neural progenitor cell differentiation during hippocampal morphogenesis. Cereb. Cortex 24 (2014) 261-79. PMID:23042739 PMC:PMC3862270

    Grabowska, M. M., A. D. Elliott, D. J. DeGraff, P. D. Anderson, G. Anumanthan, H. Yamashita, Q. Sun, D. B. Friedman, D. L. Hachey, X. Yu, J. H. Sheehan, J. M. Ahn, G. V. Raj, D. W. Piston, R. M. Gronostajski, and R. J. Matusik. NFI transcription factors interact with FOXA1 to regulate prostate-specific gene expression. Mol. Endocrinol. 28 (2014) 949-64. PMID:24801505 PMC:4042066

    Martynoga, B., J. L. Mateo, B. Zhou, J. Andersen, A. Achimastou, N. Urban, D. van den Berg, D. Georgopoulou, S. Hadjur, J. Wittbrodt, L. Ettwiller, M. Piper, R. M. Gronostajski, and F. Guillemot. Epigenomic enhancer annotation reveals a key role for NFIX in neural stem cell quiescence. Genes Dev. 27 (2013) 1769-86. PMID:23964093 PMC:3759694

    Harris, L., C. Dixon, K. Cato, Y. H. Heng, N. D. Kurniawan, J. F. Ullmann, A. L. Janke, R. M. Gronostajski, L. J. Richards, T. H. Burne, and M. Piper. Heterozygosity for nuclear factor one x affects hippocampal-dependent behaviour in mice. PLoS One 8 (2013) e65478. PMID:23776487, PMC:3679126

    Dixon, C., T. J. Harvey, A. G. Smith, R. M. Gronostajski, T. L. Bailey, and M. Piper. Nuclear Factor One X Regulates Bobby Sox During Development of the Mouse Forebrain. Cell Mol. Neurobiol, (2013) PMID:23852417,

    Ding, B., W. Wang, T. Selvakumar, H. S. Xi, H. Zhu, C. W. Chow, J. D. Horton, R. M. Gronostajski, and D. L. Kilpatrick. Temporal regulation of nuclear factor one occupancy by calcineurin/NFAT governs a voltage-sensitive developmental switch in late maturing neurons. J. Neurosci. 33 (2013) 2860-72. PMID:23407945,

    Chang, C. Y., H. A. Pasolli, E. G. Giannopoulou, G. Guasch, R. M. Gronostajski, O. Elemento, and E. Fuchs. NFIB is a governor of epithelial-melanocyte stem cell behaviour in a shared niche. Nature 495 (2013) 98-102. PMID:23389444, PMC:3635831

    Yusuf, D., S. L. Butland, M. I. Swanson, E. Bolotin, A. Ticoll, W. A. Cheung, X. Y. Zhang, C. T. Dickman, D. L. Fulton, J. S. Lim, J. M. Schnabl, O. H. Ramos, M. Vasseur-Cognet, C. N. de Leeuw, E. M. Simpson, G. U. Ryffel, E. W. Lam, R. Kist, M. S. Wilson, R. Marco-Ferreres, J. J. Brosens, L. L. Beccari, P. Bovolenta, B. A. Benayoun, L. J. Monteiro, H. D. Schwenen, L. Grontved, E. Wederell, S. Mandrup, R. A. Veitia, H. Chakravarthy, P. A. Hoodless, M. M. Mancarelli, B. E. Torbett, A. H. Banham, S. P. Reddy, R. L. Cullum, M. Liedtke, M. P. Tschan, M. Vaz, A. Rizzino, M. Zannini, S. Frietze, P. J. Farnham, A. Eijkelenboom, P. J. Brown, D. Laperriere, D. Leprince, T. de Cristofaro, K. L. Prince, M. Putker, L. del Peso, G. Camenisch, R. H. Wenger, M. Mikula, M. Rozendaal, S. Mader, J. Ostrowski, S. J. Rhodes, C. Van Rechem, G. Boulay, S. W. Olechnowicz, M. B. Breslin, M. S. Lan, K. K. Nanan, M. Wegner, J. Hou, R. D. Mullen, S. C. Colvin, P. J. Noy, C. F. Webb, M. E. Witek, S. Ferrell, J. M. Daniel, J. Park, S. A. Waldman, D. J. Peet, M. Taggart, P. S. Jayaraman, J. J. Karrich, B. Blom, F. Vesuna, H. O'Geen, Y. Sun, R. M. Gronostajski, M. W. Woodcroft, M. R. Hough, E. Chen, G. N. Europe-Finner, M. Karolczak-Bayatti, J. Bailey, O. Hankinson, V. Raman, D. P. LeBrun, S. Biswal, C. J. Harvey, J. P. DeBruyne, J. B. Hogenesch, R. F. Hevner, C. Heligon, et al. The transcription factor encyclopedia. Genome Biol. 13 (2012) R24. PMID:22458515,

    Plachez, C., K. Cato, R. C. McLeay, Y. H. Heng, T. L. Bailey, R. M. Gronostajski, L. J. Richards, A. C. Puche, and M. Piper. Expression of nuclear factor one A and -B in the olfactory bulb. J. Comp. Neurol. 520 (2012) 3135-49. PMID:22886731,

    Kilpatrick, D. L., W. Wang, R. Gronostajski, and E. D. Litwack. Nuclear factor I and cerebellar granule neuron development: an intrinsic-extrinsic interplay. Cerebellum 11 (2012) 41-9. PMID:22548229, PMC:3175246

    Kang, P., H. K. Lee, S. M. Glasgow, M. Finley, T. Donti, Z. B. Gaber, B. H. Graham, A. E. Foster, B. G. Novitch, R. M. Gronostajski, and B. Deneen. Sox9 and NFIA coordinate a transcriptional regulatory cascade during the initiation of gliogenesis. Neuron 74 (2012) 79-94. PMID:22500632,

    Heng, Y. H., R. C. McLeay, T. J. Harvey, A. G. Smith, G. Barry, K. Cato, C. Plachez, E. Little, S. Mason, C. Dixon, R. M. Gronostajski, T. L. Bailey, L. J. Richards, and M. Piper. NFIX Regulates Neural Progenitor Cell Differentiation During Hippocampal Morphogenesis. Cereb. Cortex (2012) PMID:23042739,

    Gronostajski, R. M., J. Guaneri, D. H. Lee, and S. M. Gallo. The NFI-Regulome Database: A tool for annotation and analysis of control regions of genes regulated by Nuclear Factor I transcription factors. Journal of clinical bioinformatics 1 (2011) 4.

    Piper, M., L. Harris, G. Barry, Y. H. Heng, C. Plachez, R. M. Gronostajski, and L. J. Richards. Nuclear factor one X regulates the development of multiple cellular populations in the postnatal cerebellum. J. Comp. Neurol. 519 (2011) 3532-48.

    Subramanian, L., A. Sarkar, A. S. Shetty, B. Muralidharan, H. Padmanabhan, M. Piper, E. S. Monuki, I. Bach, R. M. Gronostajski, L. J. Richards, and S. Tole. Transcription factor Lhx2 is necessary and sufficient to suppress astrogliogenesis and promote neurogenesis in the developing hippocampus. Proc. Natl. Acad. Sci. (USA) 108 (2011) E265-74.

    Meng, F., T. M. Suchyna, E. Lazakovitch, R. M. Gronostajski, and F. Sachs. Real Time FRET Based Detection of Mechanical Stress in Cytoskeletal and Extracellular Matrix Proteins. Cell Mol Bioeng 4 (2011) 148-59

    Muthusamy, N., H. C. Chen, G. Rajgolikar, K. G. Butz, F. W. Frissora, and R. M. Gronostajski. Recombination activation gene-2-deficient blastocyst complementation analysis reveals an essential role for nuclear factor I-A transcription factor in T-cell activation. Int. Immunol. 23 (2011) 385-90.

    Hsu, Y. C., J. Osinski, C. E. Campbell, E. D. Litwack, D. Wang, S. Liu, C. J. Bachurski, and R. M. Gronostajski. Mesenchymal nuclear factor I B regulates cell proliferation and epithelial differentiation during lung maturation. Dev. Biol. 354 (2011) 242-52.

    Piper, M., G. Barry, J. Hawkins, S. Mason, C. Lindwall, E. Little, A. Sarkar, A. G. Smith, R. X. Moldrich, G. M. Boyle, S. Tole, R. M. Gronostajski, T. L. Bailey, and L. J. Richards. NFIA controls telencephalic progenitor cell differentiation through repression of the Notch effector Hes1. J. Neurosci. 30 (2010) 9127-39.

    Zheng, S., S. M. Eacker, S. J. Hong, R. M. Gronostajski, T. M. Dawson, and V. L. Dawson. NMDA-induced neuronal survival is mediated through nuclear factor I-A in mice. J. Clin. Invest. 120 (2010) 2446-56.

    Wang, W., J. E. Crandall, E. D. Litwack, R. M. Gronostajski, and D. L. Kilpatrick. Targets of the nuclear factor I regulon involved in early and late development of postmitotic cerebellar granule neurons. J. Neurosci. Res. 88 (2010) 258-65.

    Messina, G., S. Biressi, S. Monteverde, A. Magli, M. Cassano, L. Perani, E. Roncaglia, E. Tagliafico, L. Starnes, C. E. Campbell, M. Grossi, D. J. Goldhamer, R. M. Gronostajski, and G. Cossu. Nfix regulates fetal-specific transcription in developing skeletal muscle. Cell 140 (2010) 554-66.

    Schneegans, T., U. Borgmeyer, M. Hentschke, R. M. Gronostajski, M. Schachner, and T. Tilling. Nuclear factor I-A represses expression of the cell adhesion molecule L1. BMC Mol Biol 10 (2009) 107.

    Piper, M., R. X. Moldrich, C. Lindwall, E. Little, G. Barry, S. Mason, N. Sunn, N. D. Kurniawan, R. M. Gronostajski, and L. J. Richards. Multiple non-cell-autonomous defects underlie neocortical callosal dysgenesis in Nfib-deficient mice. Neural Dev 4 (2009) 43.

    Whittle, C. M., E. Lazakovitch, R. M. Gronostajski, and J. D. Lieb. DNA-binding specificity and in vivo targets of Caenorhabditis elegans nuclear factor I. Proc. Natl. Acad. Sci. (USA) 106 (2009) 12049-54.

    Wang, W., J. E. Crandall, E. D. Litwack, R. M. Gronostajski, and D. L. Kilpatrick. Targets of the nuclear factor I regulon involved in early and late development of postmitotic cerebellar granule neurons. J. Neurosci. Res. (2009)

    Lee, D. S., J. T. Park, H. M. Kim, J. S. Ko, H. H. Son, R. M. Gronostajski, M. I. Cho, P. H. Choung, and J. C. Park. Nuclear factor I-C is essential for odontogenic cell proliferation and odontoblast differentiation during tooth root development. J. Biol. Chem. 284 (2009) 17293-303.

    Lee, T. Y., D. S. Lee, H. M. Kim, J. S. Ko, R. M. Gronostajski, M. I. Cho, H. H. Son, and J. C. Park. Disruption of Nfic Causes Dissociation of Odontoblasts by Interfering With the Formation of Intercellular Junctions and Aberrant Odontoblast Differentiation. J. Histochem. Cytochem. (2009)

    Kumbasar, A., C. Plachez, R. M. Gronostajski, L. J. Richards, and E. D. Litwack. Absence of the transcription factor Nfib delays the formation of the basilar pontine and other mossy fiber nuclei. J. Comp. Neurol. 513 (2009) 98-112.

    Plachez, C., C. Lindwall, N. Sunn, M. Piper, R. X. Moldrich, C. E. Campbell, J. M. Osinski, R. M. Gronostajski, and L. J. Richards. Nuclear factor I gene expression in the developing forebrain. J. Comp. Neurol. 508 (2008) 385-401.

    Mason, S., M. Piper, R. M. Gronostajski, and L. J. Richards. Nuclear Factor One Transcription Factors in CNS Development. Mol. Neurobiol. 39 (2008) 10-23.

    Lazakovitch, E., J. M. Kalb, and R. M. Gronostajski. Lifespan extension and increased pumping rate accompany pharyngeal muscle-specific expression of nfi-1 in C. elegans. Dev. Dyn. 237 (2008) 2100-7.

    Campbell, C. E., M. Piper, C. Plachez, Y. T. Yeh, J. S. Baizer, J. M. Osinski, E. D. Litwack, L. J. Richards, and R. M. Gronostajski. The transcription factor Nfix is essential for normal brain development. BMC Dev. Biol. 8 (2008) 52.

    Barry, G., M. Piper, C. Lindwall, R. Moldrich, S. Mason, E. Little, A. Sarkar, S. Tole, R. M. Gronostajski, and L. J. Richards. Specific glial populations regulate hippocampal morphogenesis. J. Neurosci. 28 (2008) 12328-40.

    Park, J. C., Y. Herr, H. J. Kim, R. M. Gronostajski, and M. I. Cho. Nfic gene disruption inhibits differentiation of odontoblasts responsible for root formation and results in formation of short and abnormal roots in mice. J. Periodontol. 78 (2007) 1795-802.

    Wong, Y. W., C. Schulze, T. Streichert, R. M. Gronostajski, M. Schachner, and T. Tilling. Gene expression analysis of nuclear factor I-A (NFI-A)-deficient mice indicates delayed brain maturation. Genome Biol. 8 (2007) R72.

    Wang, W., D. Mullikin-Kilpatrick, J. E. Crandall, R. M. Gronostajski, E. D. Litwack, and D. L. Kilpatrick. Nuclear factor I coordinates multiple phases of cerebellar granule cell development via regulation of cell adhesion molecules. J. Neurosci. 27 (2007) 6115-27.

    Lu, W., F. Quintero-Rivera, Y. Fan, F. S. Alkuraya, D. J. Donovan, Q. Xi, A. Turbe-Doan, Q. G. Li, C. G. Campbell, A. L. Shanske, E. H. Sherr, A. Ahmad, R. Peters, B. Rilliet, P. Parvex, A. G. Bassuk, D. J. Harris, H. Ferguson, C. Kelly, C. A. Walsh, R. M. Gronostajski, K. Devriendt, A. Higgins, A. H. Ligon, B. J. Quade, C. C. Morton, J. F. Gusella, and R. L. Maas. NFIA haploinsufficiency is associated with a CNS malformation syndrome and urinary tract defects. PLoS Genet 3 (2007) e80.

    Deneen, B., R. Ho, A. Lukaszewicz, C. J. Hochstim, R. M. Gronostajski, and D. J. Anderson. The transcription factor NFIA controls the onset of gliogenesis in the developing spinal cord. Neuron 52 (2006) 953-68.

    Butz, N. V., R. M. Gronostajski and C. E. Campbell. T-box proteins differentially activate the expression of the endogenous interferon gamma gene versus transfected reporter genes in non-immune cells. Gene 377:130-9, 2006.

    Lazakovitch, E., J. M. Kalb, R. Matsumoto, K. Hironoa, Y. Kohara, and R. M. Gronostajski. nfi-1 affects behavior and life-span in C. elegans but is not essential for DNA replication or survival. BMC Dev. Biol. 5:24. 2005 (contains BMC Image of the Month)

    Steele-Perkins, G., C. Plachez, K. G. Butz, G. H. Yang, C. J. Bachurski, S. L. Kinsman, E. D. Litwack, L. J. Richards and R. M. Gronostajski. The transcription factor gene Nfib is essential for both lung maturation and brain development. Mol. Cell. Biol. 25:685-98, 2005.

    Wang, W., R. E. Stock, R. M. Gronostajski, Y. W. Wong, M. Schachner, and D. L. Kilpatrick. A role for nuclear factor I in the intrinsic control of cerebellar granule neuron gene expression. J. Biol. Chem. 279:53491-7, 2004.

    Butz, N. V., C. E. Campbell, and R. M. Gronostajski.  Differential target gene activation by TBX2 and TBX2VP16: evidence for activation-domain dependent modulation of gene target specificity. Gene 342:67-76, 2004.

    Ling, G., C. R. Hauer, R. M. Gronostajski, B. Pentecost, and X. Ding. 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. 279: 27888-95, 2004.

    Bachurski, C., G. Yang, T. Currier, R. M. Gronostajski, and D. Hong. Nuclear Factor I/Thryoid Transcription Factor-1 interactions modulate Surfactant Protein-C transcription. Mol. Cell. Biol. 23: 9014-24, 2003.

    Murtagh, J., F. Martin, and R. M. Gronostajski. The Nuclear Factor I (NFI) gene family in mammary gland development and function. J. Mammary Gland Biol. Neoplasia 8: 241-54, 2003.

    Messam, C. A., J. Hou, R. M. Gronostajski, and E. O. Major. Lineage pathway of human brain progenitor cells identified by JC virus susceptability. Ann. Neurol. 53: 636-46, 2003.

    Kido, K., H. Bannert, R. M. Gronostajski, and R. M. Flugel.  Bel1-mediated Transactivation of the Spumaretroviral Internal Promoter Is Repressed by Nuclear Factor I. J. Biol. Chem. 278:11836-11842, 2003.

    Pan, L., Glenn, S.T., Jones, C.A., Gronostajski, R.M. and K.W. Gross.  Regulation of renin enhancer activity by nuclear factor I and Sp1/Sp3. Biochim. Biophys. Acta. 1625:280-90, 2003.

    Shu, T., K. G. Butz, C. Plachez, R. M. Gronostajski, and L. J. Richards.  Abnormal development of forebrain midline glia and commissural projections in Nfia knock-out mice. J. Neurosci. 23:203-12, 2003.

    Steele-Perkins, G., K. G. Butz, G. E. Lyons, M. Zeichner-David, H.-J. Kim, M. I. Cho, and R. M. Gronostajski.  Essential role for NFI-C/CTF transcription-replication factor in tooth root development. Mol. Cell. Biol. 23:1075-1084, 2003.

    Gronostajski, R.M. Nuclear Factors, In: The Encyclopedia of Molecular Medicine, Wiley Press, New York, NY pp. 2290-1, 2002.

    Gronostajski, R.M. Nuclear Factor I, In: The Encyclopedia of Molecular Medicine, Wiley Press, New York, NY pp. 2291-2, 2002.

    Majumder, S., K. Ghoshal, R.M. Gronostajski and S.T. Jacob. Downregulation of constitutive and heavy metal-induced metallothionein-I expression by nuclear factor I. Gene Expr. 9(4-5):203-15, 2001.

    Mukhopadhyay, S.S., S.L.Wyszomierski, R.M. Gronostajski and J.M. Rosen. Differential interactions of specific Nuclear Factor I isoforms with the glucocorticoid receptor and STAT5 in the cooperative regulation of WAP gene expression. Mol. Cell. Biol. 21: 6859-69, 2001.

    Gronostajski, R.M. Roles of the NFI/CTF gene family in transcription and development. Gene 249: 31-45, 2000.

    Behrens, M., G. Venkatraman, R.M. Gronostajski, R.R. Reed and F.L. Margolis. NFI in the development of the olfactory neuroepithelium and the regulation of olfactory marker protein gene expression. Eur. J. Neurosci. 12:1372-84, 2000.

    Baumeister, H., R.M. Gronostajski, G.E. Lyons and F.L. Margolis. Identification of NFI-binding sites and cloning of NFI-cDNAs suggest a regulatory role for NFI transcription factors in olfactory neuron gene expression. Mol. Brain. Res. 72: 65-79, 1999.

    das Neves, L., C. Duchala, F. Godinho, M. Haxhiu, C. Colmenares, W. Macklin, C.E. Campbell, K. Butz and R.M. Gronostajski.  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. (USA) 96: 11946-51, 1999.

    Fletcher, C.F., N.A. Jenkins, N.G. Copeland, A.Z. Chaudhry and R.M. Gronostajski.  Exon structure of the Nuclear Factor I DNA-binding domain from C. elegans to mammals.  Mammalian Genome 10: 390-396, 1999.

    Leahy, P., D.R. Crawford, G. Grossman, R.M. Gronostajski and R.W. Hanson.  CREB binding protetin coordinates the function of multiple transcription factors including Nuclear Factor I to regulate phosphoenolpyruvate carboxykinage (GTP) gene transcription. J. Biol. Chem. 274: 8813-8822, 1999.

    Chaudhry, A.Z., A. Vitullo and R.M. Gronostajski. 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. 274: 7072-7081, 1999.

    Chaudhry, A.Z, A. Vitullo and R.M. Gronostajski. Nuclear Factor I (NFI) isoforms differentially activate simple versus complex NFI-responsive promoters. J. Biol. Chem. 273: 18538-18546, 1998.

    Crawford, D., P. Leahy, C. Hu, A. Chaudhry, R. Gronostajski, G. Grossman, J. Woods, P. Hakimi, W. Roesler and R.W. Hanson. Nuclear Factor I regulates expression of the gene for phoshoenolpyruvate carboxykinase (GTP). J. Biol. Chem. 273: 13387-13390, 1998.

    Bandyopadhyay, S., D.W. Starke, J.J. Mieyal and R.M. Gronostajski. Thioltransferase (Glutaredoxin) Reactivates the DNA-binding Activity of Oxidation-inactivated Nuclear Factor I. J. Biol. Chem. 273: 392-397, 1998.

    Chaudhry, A.Z., G.E. Lyons and R.M. Gronostajski.  Expression patterns of the four Nuclear Factor I genes during mouse embryogenesis indicate a potential role in development. Developmental Dynamics 208: 313-325, 1997.

    Golden Oldies:

    Gronostajski, R. M., K. Nagata and J. Hurwitz. Isolation of human DNA sequences that bind to nuclear factor I, a host protein involved in adenovirus DNA replication. Proc. Natl. Acad. Sci. (USA) 81:4013-7, 1984.

    RMG picture Welcome from Rich Gronostajski (video)


    The State University of New York at Buffalo
    Dept. of Biochemistry, Developmental Genomics Group

    Genetics, Genomics & Bioinformatics Graduate Program
    New York State Center of Excellence in Bioinformatics and Life Sciences
    701 Ellicott St.

    Buffalo, New York 14203
     Telephone : (716) 829-3471

    The Sky from Buffalo

    The Sky from Buffalo

    Authored by Rich Gronostajski

    This page last updated Sept. 26th, 2016.

    Click the logo to go to:

    UB logo COEBLS logo