This study was supported by Public Service grants AA07611, AA10707, and CA58947 and the Arthritis Foundation. We gratefully acknowledge W. Biddison, National Institute for Neurological Disorders and Stroke, National Institutes of Health, MD, U.S.A., for P815-HTR cells. We are grateful to E. J. Neufeld, Harvard University, Boston, MA, U.S.A., for anti-CDP antiserum. We also express our gratitude to D. F. Gordon, University of Colorado Health Sciences Center, Denver, CO, U.S.A., and S. H. Orkin, Harvard University, Boston, MA, U.S.A., for the hGATA-2 expression plasmid. We thank Dr. Ann Roman, Indiana University School of Medicine, Indianapolis, IN, U.S.A., for critical reading of the manuscript.

  • 1
    Andres V., Nadal-Ginard B., Mahdavi V. (1992) Clox, a mammalian homeobox gene related to Drosophila cut, encodes DNA-binding regulatory proteins differentially expressed during development.Development 116,321334.
  • 2
    Andres V., Chiara M.D., Mahdavi V. (1994) A new bipartite DNA-binding domain : cooperative interaction between the cut repeat and homeo domain of the cut homeo proteins.Genes Dev. 8,245257.
  • 3
    Aufiero B., Neufeld E.J., Orkin S.H. (1994) Sequence-specific DNA binding of individual cut repeats of the human CCAAT displacement/cut homeodomain protein.Proc. Natl. Acad. Sci. USA 91,77577761.
  • 4
    Ausubel F.M., Brent R., Kingston R.E., Moore D.D., Seidman J.G., Smith J.A., Struhl K. , eds (1994) Methylation and uracil interference assays for analysis of protein-DNA interactions, inCurrent Protocols in Molecular Biology, pp. 12.13.1112.13.17. Green Publishing Associates and John Wiley and Sons, New York.
  • 5
    Banan M., Rojas I.C., Lee W.H., King H.L., Harriss J.V., Kobayashi R., Webb C.F., Gottlieb P.D. (1997) Interaction of the nuclear matrix-associated region (MAR)-binding proteins, SATB1 and CDP/Cux, with a MAR element (L2a) in an upstream regulatory region of the mouse CD8a gene.J. Biol. Chem. 272,1844018452.
  • 6
    Barberis A., Superti-Furga G., Busslinger M. (1987) Mutually exclusive interaction of the CCAAT-binding factor and of a displacement protein with overlapping sequences of a histone gene promoter.Cell 50,347359.
  • 7
    Blier P. & De Montigny C. (1994) Current advances and trends in the treatment of depression.Trends Pharmacol. Sci. 15,220226.
  • 8
    Boularand S., Darmon M.C., Ravassard P., Mallet J. (1995) Characterization of the human tryptophan hydroxylase gene promoter. Transcriptional regulation by cAMP requires a new motif distinct from the cAMP-responsive element.J. Biol. Chem. 270,37573764.
  • 9
    Crow T.J., Baker H.F., Cross A.J., Joseph M.H., Lofthouse R., Longden A., Owen F., Riley G.J., Glover V., Killpack W.S. (1979) Monoamine mechanisms in chronic schizophrenia : post-mortem neurochemical findings.Br. J. Psychiatry 134,249256.
  • 10
    Deguchi T. (1977) Tryptophan hydroxylase in pineal gland of rat : postsynaptic localization and absence of circadian change.J. Neurochem. 28,667668.
  • 11
    DeVeaugh-Geiss J. (1993) Diagnosis and treatment of obsessive compulsive disorder.Annu. Rev. Med. 44,5361.
  • 12
    Dorfman D.M., Wilson D.B., Bruns G.A., Orkin S.H. (1992) Human transcription factor GATA-2. Evidence for regulation of preproendothelin-1 gene expression in endothelial cells.J. Biol. Chem. 267,12791285.
  • 13
    Dufort D. & Nepveu A. (1994) The human cut homeodomain protein represses transcription from the c-myc promoter.Mol. Cell. Biol. 14,42514257.
  • 14
    Gershon M.D., Dreyfus C.F., Pickel V.M., Joh T.H., Reis D.J. (1977) Serotonergic neurons in the peripheral nervous system : identification in gut by immunohistochemical localization of tryptophan hydroxylase.Proc. Natl. Acad. Sci. USA 74,30863089.
  • 15
    Gordon D.F., Lewis S.R., Haugen B.R., James R.A., McDermott M.T., Wood W.M., Ridgway E.C. (1997) Pit-1 and GATA-2 interact and functionally cooperate to activate the thyrotropin beta-subunit promoter.J. Biol. Chem. 272,2433924347.
  • 16
    Gorski K., Carneiro M., Schibler U. (1986) Tissue-specific in vitro transcription from the mouse albumin promoter.Cell 47,767776.
  • 17
    Graham F.L. & Van Der Eb A.J. (1973) A new technique for the assay of infectivity of human adenovirus 5 DNA.Virology 52,456467.
  • 18
    Grahame-Smith D.G. (1964) Tryptophan hydroxylation in brain.Biochem. Biophys. Res. Commun. 16,586592.
  • 19
    Harada R., Berube G., Tamplin O.J., Denis-Larose C., Nepveu A. (1995) DNA-binding specificity of the cut repeats from the human cut-like protein.Mol. Cell. Biol. 15,129140.
  • 20
    Higgy N.A., Tarnasky H.A., Valarche I., Nepveu A., Van Der Hoorn F.A. (1997) Cux/CDP homeodomain protein binds to an enhancer in the rat c-mos locus and represses its activity.Biochim. Biophys. Acta 1351,313324.
  • 21
    Higuchi R. (1989) Using PCR to engineer DNA, inPCR Technology : Principles and Applications for DNA Amplification (Erlich H. A., ed), pp. 6170. Stockton Press, New York.
  • 22
    Huh S.O., Park D.H., Cho J.Y., Joh T.H., Son J.H. (1994) A 6.1 kb 5′ upstream region of the mouse tryptophan hydroxylase gene directs expression of E. coli lacZ to major serotonergic brain regions and pineal gland in transgenic mice.Mol. Brain Res. 24,145152.
  • 23
    Jequier E., Lovenberg W., Sjoerdsma A. (1967) Tryptophan hydroxylase inhibition : the mechanism by which p-chlorophenylalanine depletes rat brain serotonin. Mol. Pharmacol. 3,274278.
  • 24
    Khanna-Gupta A., Zibello T., Kolla S., Neufeld J., Berlinder N. (1997) CCAAT displacement protein (CDP/Cut) recognizes a silencer element within the lactoferin gene promoter.Blood 90,27842795.
  • 25
    Korpi E.R., Kleinman J.E., Goodman S.I., Phillips I., DeLisi L.E., Linnoila M., Wyatt R.J. (1986) Serotonin and 5-hydroxyindoleacetic acid in brains of suicide victims. Comparison in chronic schizophrenic patients with suicide as cause of death.Arch. Gen. Psychiatry 43,594600.
  • 26
    Kuhar M.J., Aghajanian G.K., Roth R.H. (1972) Tryptophan hydroxylase activity and synaptosomal uptake of serotonin in discrete brain regions after midbrain raphe lesions : correlations with serotonin levels and histochemical fluorescence.Brain Res. 44,165176.
  • 27
    Legacy C., Faudon M., Hery F., Ternaux J.P. (1983) 5-HT metabolism in the intestinal wall of the rat. I. The mucosa.Neurochem. Int. 5,721727.
  • 28
    Lovenberg W., Levine R.J., Sjoerdsma A. (1965) A tryptophan hydroxylase in cell-free extracts of malignant mouse mast cells.Biochem. Pharmacol. 14,887889.
  • 29
    Luo W. & Skalnik D.G. (1996) CCAAT displacement protein competes with multiple transcriptional activators for binding to four sites in the proximal gp91 phox promoter.J. Biol. Chem. 271,1820318210.
  • 30
    Mailly F., Berube G., Harada R., Mao P.L., Phillips S., Nepveu A. (1996) The human cut homeodomain protein can repress gene expression by two distinct mechanisms : active repression and competition for binding site occupancy.Mol. Cell. Biol. 16,53465357.
  • 31
    Martin D.I., Zon L.I., Mutter G., Orkin S.H. (1990) Expression of an erythroid transcription factor in megakaryocytic and mast cell lineages.Nature 344,444447.
  • 32
    McDonagh K.T. & Nienhuis A.W. (1991) Induction of the human γ-globin gene promoter in K562 cells by sodium butyrate : reversal of repression by CCAAT displacement protein. Blood 78,255a.
  • 33
    Neufeld E.J., Skalnik D.G., Lievens P.M., Orkin S.H. (1992) Human CCAAT displacement protein is homologous to the Drosophila homeoprotein, cut.Nat. Genet. 1,5055.
  • 34
    Nordeen S.K. (1988) Luciferase reporter gene vectors for analysis of promoters and enhancers.Biotechniques 6,454458.
  • 35
    Omichinski J.G., Clore G.M., Schaad O., Felsenfeld G., Trainor C., Appella E., Stahl S.J., Gronenborn A.M. (1993) NMR structure of a specific DNA complex of Zn-containing DNA binding domain of GATA-1.Science 261,438446.
  • 36
    Reed G.E., Kirchner J.E., Carr L.G. (1995) NF-Y activates mouse tryptophan hydroxylase transcription.Brain Res. 682,112.
  • 37
    Ronchi A., Bellorini M., Mongelli N., Mantovani R. (1995) CCAAT-box binding protein NF-Y (CBF, CP1) recognizes the minor groove and distorts DNA.Nucleic Acids Res. 23,45654572.
  • 38
    Sato T.L., Jequier E., Lovenberg W., Sjoerdsma A. (1967) Characterization of a tryptophan hydroxylating enzyme from malignant mouse mast cell.Eur. J. Pharmacol. 1,1825.
  • 39
    Sellers E.M., Higgins G.A., Sobell M.B. (1992) 5-HT and alcohol abuse.Trends Pharmacol. Sci. 13,6975.
  • 40
    Shapiro D.J., Sharp P.A., Wahli W.W., Keller M.J. (1988) A high-efficiency HeLa cell nuclear transcription extract.DNA 7,4755.
  • 41
    Skalnik D.G., Strauss E.C., Orkin S.H. (1991) CCAAT displacement protein as a repressor of the myelomonocytic-specific gp91-phox gene promoter.J. Biol. Chem. 266,1673616744.
  • 42
    Song C.S., Jung M.H., Chen S., Chatterjee B. (1997) A rapid one-step procedure for preparation of G plus A sequence markers by acid-induced apurinization and DNA cleavage.Elsevier Trends Journals Technical Tips Online : T40074.
  • 43
    Teerawatanasuk N. & Carr L.G. (1998) CBF/NF-Y activates transcription of the human tryptophan hydroxylase gene through an inverted CCAAT box.Mol. Brain Res. 55,6170.
  • 44
    Thomas K.B. & Invone P.M. (1991) Circadian rhythm of tryptophan hydroxylase activity in chicken retina.Cell. Mol. Neurobiol. 11,511527.
  • 45
    Tong J.H. & Kaufman S. (1975) Tryptophan hydroxylase. Purification and some properties of the enzyme from rabbit hindbrain.J. Biol. Chem. 250,41524158.
  • 46
    Valarche I., Tissier-Seta J.P., Hirsch M.R., Martinez S., Goridis C., Brunet J.F. (1993) The mouse homeodomain protein Phox2 regulates Ncam promoter activity in concert with Cux/CDP and is a putative determinant of neurotransmitter phenotype.Development 119,881896.
  • 47
    Whyatt D.J., De Boer E., Grosveld F. (1993) The two zinc fingerlike domains of GATA-1 have different DNA binding specificities.EMBO J. 12,49935005.
  • 48
    Yoon S.O. & Chikaraishi D.M. (1994) Isolation of two E-box binding factors that interact with the rat tyrosine hydroxylase enhancer.J. Biol. Chem. 269,1845318462.
  • 49
    Zon L.I., Gurish M.F., Stevens R.L., Mather C., Reynolds D.S., Austen K.F., Orkin S.H. (1991) GATA-binding transcription factors in mast cells regulate the promoter of the mast cell carboxypeptidase A gene.J. Biol. Chem. 266,2294822953.