TG-interacting Factor (TGIF) Downregulates SOX3 Gene Expression in the NT2/D1 Cell Line

Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, PO Box 23, 11010 Belgrade, Serbia

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Corresponding author: E-mail address: mojsin@eunet.rs (Marija Mojsin)

摘要

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Abstract: SOX3 is a member of the Sox gene family implicated in brain formation and cognitive function. It is considered to be one of the earliest neural markers in vertebrates, playing a role in specifying neuronal fate. Recently, we have established the first link between TALE (three-amino-acid loop extension) proteins, PBX1 (pre-B-cell leukemia homeobox 1) and MEIS1 (myeloid ecotropic viral integration site 1 homologue), and the expression of the human SOX3 gene. Here we present the evidence that TGIF (TG-interacting factor) is an additional TALE superfamily member involved in the regulation of human SOX3 gene expression in NT2/D1 cells by direct interaction with the consensus binding site that is conserved in primate orthologue promoters. Functional analysis demonstrated that mutation of the TGIF binding site resulted in the activation of SOX3 promoter. TGIF overexpression downregulates SOX3 promoter activity and decreases endogenous SOX3 protein expression in both uninduced and retinoic acid (RA)-induced NT2/D1 cells. Up to now, this is the first transcription factor identified as a negative regulator of SOX3 gene expression. The obtained results further underscore the significance of TALE proteins as important transcriptional regulators ofSOX3 gene expression.
- NT2/D1 cells /
- TGIF /
- Retinoic acid

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参考文献(43)

[1]	Andrews, P.W. Dev. Biol., 103 (1984),pp. 285-293
[2]	Andrews, P.W. Human teratocarcinomas Biochim. Biophys. Acta, 948 (1988),pp. 17-36
[3]	Argyropoulos, G., Rankinen, T., Bai, F. et al. The agouti-related protein and body fatness in humans Int. J. Obes. Relat. Metab. Disord., 27 (2003),pp. 276-280
[4]	Bartholin, L., Powers, S.E., Melhuish, T.A. et al. TGIF inhibits retinoid signaling Mol. Cell. Biol., 26 (2006),pp. 990-1001
[5]	Bertolino, E., Reimund, B., Wildt-Perinic, D. et al. A novel homeobox protein which recognizes a TGT core and functionally interferes with a retinoid-responsive motif J. Biol. Chem., 270 (1995),pp. 31178-31188
[6]	Bertolino, E., Wildt, S., Richards, G. et al. Expression of a novel murine homeobox gene in the developing cerebellar external granular layer during its proliferation Dev. Dyn., 205 (1996),pp. 410-420
[7]	Brunelli, S., Silva Casey, E., Bell, D. et al. Expression of Sox3 throughout the developing central nervous system is dependent on the combined action of discrete, evolutionarily conserved regulatory elements Genesis, 36 (2003),pp. 12-24
[8]	Cartharius, K., Frech, K., Grote, K. et al. MatInspector and beyond: promoter analysis based on transcription factor binding sites Bioinformatics, 21 (2005),pp. 2933-2942
[9]	Collignon, J., Sockanathan, S., Hacker, A. et al. A comparison of the properties of Sox-3 with Sry and two related genes, Sox-1 and Sox-2 Development, 122 (1996),pp. 509-520
[10]	Dignam, J.D., Lebovitz, R.M., Roeder, R.G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei Nucleic Acids Res., 11 (1983),pp. 1475-1489
[11]	El-Jaick, K.B., Powers, S.E., Bartholin, L. et al. Functional analysis of mutations in TGIF associated with holoprosencephaly Mol. Genet. Metab., 90 (2007),pp. 97-111
[12]	Golden, J.A. Holoprosencephaly: a defect in brain patterning J. Neuropathol. Exp. Neurol., 57 (1998),pp. 991-999
[13]	Gongal, P.A., Waskiewicz, A.J. Zebrafish model of holoprosencephaly demonstrates a key role for TGIF in regulating retinoic acid metabolism Hum. Mol. Genet., 17 (2008),pp. 525-538
[14]	Gripp, K.W., Wotton, D., Edwards, M.C. et al. Mutations in TGIF cause holoprosencephaly and link NODAL signalling to human neural axis determination Nat. Genet., 25 (2000),pp. 205-208
[15]	Houldsworth, J., Heath, S.C., Bosl, G.J. et al. Expression profiling of lineage differentiation in pluripotential human embryonal carcinoma cells Cell Growth Differ., 13 (2002),pp. 257-264
[16]	Irrthum, A., Devriendt, K., Chitayat, D. et al. Am. J. Hum. Genet., 72 (2003),pp. 1470-1478
[17]	Jabet, C., Gitti, R., Summers, M.F. et al. NMR studies of the pbx1 TALE homeodomain protein free in solution and bound to DNA: proposal for a mechanism of HoxB1-Pbx1-DNA complex assembly J. Mol. Biol., 291 (1999),pp. 521-530
[18]	Jacobs, Y., Schnabel, C.A., Cleary, M.L. Trimeric association of Hox and TALE homeodomain proteins mediates Hoxb2 hindbrain enhancer activity Mol. Cell. Biol., 19 (1999),pp. 5134-5142
[19]	Kamachi, Y., Uchikawa, M., Kondoh, H. Pairing SOX off: with partners in the regulation of embryonic development Trends Genet., 16 (2000),pp. 182-187
[20]	Kantaputra, P.N., Limwongse, C., Tochareontanaphol, C. et al. Contiguous gene syndrome of holoprosencephaly and hypotrichosis simplex: association with an 18p11.3 deletion Am. J. Med. Genet. A, 140 (2006),pp. 2598-2602
[21]	Knepper, J.L., James, A.C., Ming, J.E. Dev. Dyn., 235 (2006),pp. 1482-1490
[22]	Knoepfler, P.S., Lu, Q., Kamps, M.P. Pbx-1 Hox heterodimers bind DNA on inseparable half-sites that permit intrinsic DNA binding specificity of the Hox partner at nucleotides 3′ to a TAAT motif Nucleic Acids Res., 24 (1996),pp. 2288-2294
[23]	Kovacevic Grujicic, N., Mojsin, M., Krstic, A. et al. Gene, 344 (2005),pp. 287-297
[24]	Krstic, A., Mojsin, M., Stevanovic, M. Arch. Biochem. Biophys., 467 (2007),pp. 163-173
[25]	Melhuish, T.A., Gallo, C.M., Wotton, D. TGIF2 interacts with histone deacetylase 1 and represses transcription J. Biol. Chem., 276 (2001),pp. 32109-32114
[26]	Melhuish, T.A., Wotton, D. J. Biol. Chem., 275 (2000),pp. 39762-39766
[27]	Mojsin, M., Grujicic, N.K., Nikcevic, G. et al. Neurosci. Res., 56 (2006),pp. 409-418
[28]	Mojsin, M., Stevanovic, M. Biochem. J., 425 (2010),pp. 107-116
[29]	Muenke, M., Beachy, P.A. Genetics of ventral forebrain development and holoprosencephaly Curr. Opin. Genet. Dev., 10 (2000),pp. 262-269
[30]	Nikcevic, G., Savic, T., Kovacevic-Grujicic, N. et al. J. Neurochem., 107 (2008),pp. 1206-1215
[31]	Olsen, C.L., Hughes, J.P., Youngblood, L.G. et al. Epidemiology of holoprosencephaly and phenotypic characteristics of affected children: New York State, 1984-1989 Am. J. Med. Genet., 73 (1997),pp. 217-226
[32]	Pevny, L.H., Lovell-Badge, R. Sox genes find their feet Curr. Opin. Genet. Dev., 7 (1997),pp. 338-344
[33]	Sapin, V., Bouillet, P., Oulad-Abdelghani, M. et al. Differential expression of retinoic acid-inducible (Stra) genes during mouse placentation Mech. Dev., 92 (2000),pp. 295-299
[34]	Sharma, M., Sun, Z. 5′TG3′ interacting factor interacts with Sin3A and represses AR-mediated transcription Mol. Endocrinol., 15 (2001),pp. 1918-1928
[35]	Stevanovic, M. Mol. Biol. Rep., 30 (2003),pp. 127-132
[36]	Stevanovic, M., Lovell-Badge, R., Collignon, J. et al. Hum. Mol. Genet., 2 (1993),pp. 2013-2018
[37]	Weiss, J., Meeks, J.J., Hurley, L. et al. Sox3 is required for gonadal function, but not sex determination, in males and females Mol. Cell. Biol., 23 (2003),pp. 8084-8091
[38]	Won, J., Yim, J., Kim, T.K. J. Biol. Chem., 277 (2002),pp. 38230-38238
[39]	Woods, K.S., Cundall, M., Turton, J. et al. Over- and underdosage of SOX3 is associated with infundibular hypoplasia and hypopituitarism Am. J. Hum. Genet., 76 (2005),pp. 833-849
[40]	Wotton, D., Knoepfler, P.S., Laherty, C.D. et al. The Smad transcriptional corepressor TGIF recruits mSin3 Cell Growth Differ., 12 (2001),pp. 457-463
[41]	Wotton, D., Lo, R.S., Lee, S. et al. A Smad transcriptional corepressor Cell, 97 (1999),pp. 29-39
[42]	Wotton, D., Lo, R.S., Swaby, L.A. et al. Multiple modes of repression by the Smad transcriptional corepressor TGIF J. Biol. Chem., 274 (1999),pp. 37105-37110
[43]	Yang, Y., Hwang, C.K., D’Souza, U.M. et al. Three-amino acid extension loop homeodomain proteins Meis2 and TGIF differentially regulate transcription J. Biol. Chem., 275 (2000),pp. 20734-20741