Gene Symbol: Sp4
Description: trans-acting transcription factor 4
Alias: 5730497N03Rik, HF-1b, HF1-b, transcription factor Sp4
Species: mouse
Products:     Sp4

Top Publications

  1. Zhou X, Qyang Y, Kelsoe J, Masliah E, Geyer M. Impaired postnatal development of hippocampal dentate gyrus in Sp4 null mutant mice. Genes Brain Behav. 2007;6:269-76 pubmed
    b>Sp4, a member of the Sp1 family of transcription factors, is expressed restrictively in the developing nervous system and abundantly in the hippocampus...
  2. Supp D, Witte D, Branford W, Smith E, Potter S. Sp4, a member of the Sp1-family of zinc finger transcription factors, is required for normal murine growth, viability, and male fertility. Dev Biol. 1996;176:284-99 pubmed
    ..This gene, previously identified in rats and humans and designated sp4, is homologous to the Drosophila buttonhead (btd) gene, which is expressed in the head region of developing flies...
  3. Zhou X, Long J, Geyer M, Masliah E, Kelsoe J, Wynshaw Boris A, et al. Reduced expression of the Sp4 gene in mice causes deficits in sensorimotor gating and memory associated with hippocampal vacuolization. Mol Psychiatry. 2005;10:393-406 pubmed
    HF-1B/SP4:, a member of the Sp1 family of transcription factors, is expressed restrictively in the developing nervous system and most abundantly in adult hippocampus in mice...
  4. Young J, Kamenski M, Higa K, Light G, Geyer M, ZHOU X. GlyT-1 Inhibition Attenuates Attentional But Not Learning or Motivational Deficits of the Sp4 Hypomorphic Mouse Model Relevant to Psychiatric Disorders. Neuropsychopharmacology. 2015;40:2715-26 pubmed publisher
    ..The transcription factor Specificity Protein 4 (SP4) is important for neurodevelopment and is genetically associated with both schizophrenia and bipolar disorder...
  5. Johar K, Priya A, Dhar S, Liu Q, Wong Riley M. Neuron-specific specificity protein 4 bigenomically regulates the transcription of all mitochondria- and nucleus-encoded cytochrome c oxidase subunit genes in neurons. J Neurochem. 2013;127:496-508 pubmed publisher
    ..However, we discovered recently that in primary neurons, it is Sp4 and not Sp1 that regulates some of the key glutamatergic receptor subunit genes...
  6. Priya A, Johar K, Wong Riley M. Specificity protein 4 functionally regulates the transcription of NMDA receptor subunits GluN1, GluN2A, and GluN2B. Biochim Biophys Acta. 2013;1833:2745-2756 pubmed publisher
    ..Specificity protein (Sp) is a family of transcription factors that bind to GC-rich regions, with Sp1, Sp3, and Sp4 all binding to the same cis- motifs...
  7. Ji B, Wang X, Pinto Duarte A, Kim M, Caldwell S, Young J, et al. Prolonged Ketamine Effects in Sp4 Hypomorphic Mice: Mimicking Phenotypes of Schizophrenia. PLoS ONE. 2013;8:e66327 pubmed publisher
    ..Here, we examined the responses of Sp4 hypomorphic mice to NMDAR antagonists in electroencephalography and various behavioral paradigms...
  8. Ma L, Song L, Radoi G, Harrison N. Transcriptional regulation of the mouse gene encoding the alpha-4 subunit of the GABAA receptor. J Biol Chem. 2004;279:40451-61 pubmed
    ..Both Sp3 and Sp4 transcription factors can interact with the two Sp1 binding sites within the minimal promoter and are critical for ..
  9. St Amand T, Lu J, Zamora M, Gu Y, Stricker J, Hoshijima M, et al. Distinct roles of HF-1b/Sp4 in ventricular and neural crest cells lineages affect cardiac conduction system development. Dev Biol. 2006;291:208-17 pubmed
    ..Therefore, in this study, we document that a single transcription factor, HF-1b, acts through two separate cell types to direct distinct functions of the cardiac conduction system. ..

More Information


  1. Wegener A, Küspert M, Sock E, Philipsen S, Suske G, Wegner M. Sp2 is the only glutamine-rich specificity protein with minor impact on development and differentiation in myelinating glia. J Neurochem. 2017;140:245-256 pubmed publisher
    ..We also studied glia-specific conditional Sp2- and constitutive Sp4-deficient mice to include all related glutamine-rich Sp factors into our analysis...
  2. ZHOU X, Tang W, Greenwood T, Guo S, He L, Geyer M, et al. Transcription factor SP4 is a susceptibility gene for bipolar disorder. PLoS ONE. 2009;4:e5196 pubmed publisher
    The Sp4 transcription factor plays a critical role for both development and function of mouse hippocampus. Reduced expression of the mouse Sp4 gene results in a variety of behavioral abnormalities relevant to human psychiatric disorders...
  3. Lerner L, Peng G, Gribanova Y, Chen S, Farber D. Sp4 is expressed in retinal neurons, activates transcription of photoreceptor-specific genes, and synergizes with Crx. J Biol Chem. 2005;280:20642-50 pubmed
    ..molecular mechanisms of photoreceptor-specific gene transcription, we examined the role of the neuronal-enriched Sp4 nuclear protein in transcription from the rod-specific beta-PDE and rod opsin gene promoters and compared it to the ..
  4. Hammer F, Compagnone N, Vigne J, Bair S, Mellon S. Transcriptional regulation of P450scc gene expression in the embryonic rodent nervous system. Endocrinology. 2004;145:901-12 pubmed
    ..Members of the Sp family of transcription factors also bind to the same DNA sequence as Ku. Sp4 and Sp2 colocalize with P450scc in the nervous system early in development, whereas Sp1 and Sp4 colocalize later in ..
  5. Jin P, Sun Y, Grabowski G. In vivo roles of RORalpha and Sp4 in the regulation of murine prosaposin gene. DNA Cell Biol. 2001;20:781-9 pubmed
    ..In vitro, the CNS-expressed proteins Sp4 and RORalpha bind to Sp1 and RORE sites within a 310-bp fragment directly upstream of the transcription start site...
  6. Hewett K, Norman L, Sedmera D, Barker R, Justus C, Zhang J, et al. Knockout of the neural and heart expressed gene HF-1b results in apical deficits of ventricular structure and activation. Cardiovasc Res. 2005;67:548-60 pubmed
  7. Dreveny I, Kondo H, Uchiyama K, Shaw A, Zhang X, Freemont P. Structural basis of the interaction between the AAA ATPase p97/VCP and its adaptor protein p47. EMBO J. 2004;23:1030-9 pubmed
    ..We also propose a classification for ubiquitin-like domains containing or lacking a longer S3/S4 loop. ..
  8. Gollner H, Bouwman P, Mangold M, Karis A, Braun H, Rohner I, et al. Complex phenotype of mice homozygous for a null mutation in the Sp4 transcription factor gene. Genes Cells. 2001;6:689-97 pubmed
    b>Sp4 is a zinc finger transcription factor which is closely related to Sp1 and Sp3. All three proteins recognize the same DNA elements and can act as transcriptional activators through glutamine-rich activation domains...
  9. Priya A, Johar K, Nair B, Wong Riley M. Specificity protein 4 (Sp4) regulates the transcription of AMPA receptor subunit GluA2 (Gria2). Biochim Biophys Acta. 2014;1843:1196-206 pubmed publisher
    ..The goal of the present study was to test our hypothesis that Sp-factors (Sp1, Sp3, and/or Sp4) also regulate AMPA subunit genes...
  10. ZHOU X, Nie Z, Roberts A, Zhang D, Sebat J, Malhotra D, et al. Reduced NMDAR1 expression in the Sp4 hypomorphic mouse may contribute to endophenotypes of human psychiatric disorders. Hum Mol Genet. 2010;19:3797-805 pubmed publisher
    The reduced expression of the Sp4 gene in Sp4 hypomorphic mice resulted in subtle vacuolization in the hippocampus as well as deficits in sensorimotor gating and contextual memory, putative endophenotypes for schizophrenia and other ..
  11. Saia G, Lalonde J, Sun X, Ramos B, Gill G. Phosphorylation of the transcription factor Sp4 is reduced by NMDA receptor signaling. J Neurochem. 2014;129:743-52 pubmed publisher
    ..The transcription factor Sp4 regulates the developmental patterning of dendrites, contributes to complex processes including learning ..
  12. Sun X, Pinacho R, Saia G, Punko D, Meana J, Ramos B, et al. Transcription factor Sp4 regulates expression of nervous wreck 2 to control NMDAR1 levels and dendrite patterning. Dev Neurobiol. 2015;75:93-108 pubmed publisher
    ..Mice mutant for the transcription factor Sp4 have reduced levels of NMDAR subunit 1 (NR1) protein, but not mRNA, and exhibit behavioral and memory ..
  13. Song J, Mangold M, Suske G, Geltinger C, Kanazawa I, Sun K, et al. Characterization and promoter analysis of the mouse gene for transcription factor Sp4. Gene. 2001;264:19-27 pubmed
    b>Transcription factor Sp4 is a member of the Sp1 family. It functions differently from other members of this family, such as Sp1 and Sp3, and the gene for Sp4 is transcribed in a tissue-specific manner...
  14. Higa K, Ji B, Buell M, Risbrough V, Powell S, Young J, et al. Restoration of Sp4 in Forebrain GABAergic Neurons Rescues Hypersensitivity to Ketamine in Sp4 Hypomorphic Mice. Int J Neuropsychopharmacol. 2015;18:pyv063 pubmed publisher
    ..The genes and neurons that regulate behavioral responses to ketamine, however, remain poorly understood. Sp4 is a transcription factor for which gene expression is restricted to neuronal cells in the brain...
  15. Nguyêñ Trân V, Kubalak S, Minamisawa S, Fiset C, Wollert K, Brown A, et al. A novel genetic pathway for sudden cardiac death via defects in the transition between ventricular and conduction system cell lineages. Cell. 2000;102:671-82 pubmed
    ..These studies identify a novel genetic pathway for sudden cardiac death via defects in the transition between ventricular and conduction system cell lineages. ..