Germ cell nuclear factor directly represses the transcription of peroxisome proliferator-activated receptor delta gene
Chengqiang He
College of Life Science, Shandong Normal University, Jinan 250014, China
Search for more papers by this authorCorresponding Author
Naizheng Ding
School of Biological Science and Technology, Central South University, Changsha 410012, China
College of Life Science, Peking University, Beijing 100871, China
*Corresponding author: Tel, 86-731-2650230; E-mail, [email protected]Search for more papers by this authorJie Kang
Department of Biology, Shangqiu Normal University, Shangqiu 476000, China
Search for more papers by this authorChengqiang He
College of Life Science, Shandong Normal University, Jinan 250014, China
Search for more papers by this authorCorresponding Author
Naizheng Ding
School of Biological Science and Technology, Central South University, Changsha 410012, China
College of Life Science, Peking University, Beijing 100871, China
*Corresponding author: Tel, 86-731-2650230; E-mail, [email protected]Search for more papers by this authorJie Kang
Department of Biology, Shangqiu Normal University, Shangqiu 476000, China
Search for more papers by this authorThis work was supported by grants from the National Natural Science Foundation of China (No. 30400039) and the Chinese Postdoctoral Foundation (No. 2003033069 and 2004036001)
Abstract
Germ cell nuclear factor (GCNF) is a transcription factor that can repress gene transcription and plays an important role during spermatogenesis. Peroxisome proliferator-activated receptor delta (PPARδ) is a nuclear hormone receptor belonging to the steroid receptor superfamily. It can activate the expression of many genes, including those involved in lipid metabolism. In this report, we showed that GCNF specifically interacts with PPARδ promoter. Overexpression of GCNF in African green monkey SV40-transformed kidney fibroblast COS7 cells and mouse embryo fibroblast NIH 3T3 cells represses the activity of PPARδ promoter. The mutation of GCNF response element inPPARδ promoter relieves the repression in NIH 3T3 cells and mouse testis. Moreover, we showed that GCNF in nuclear extracts of mouse testis is able to bind to PPARδ promoter directly. We also found that GCNFand PPARδ mRNA were expressed with different patterns in mouse testis by in situ hybridization. These results suggested that GCNF might be a negative regulator of PPARδ gene expression through its direct interaction with PPARδ promoter in mouse testis.
References
- 1 Guan Y, Breyer MD. Peroxisome proliferator-activated receptors (PPARs): novel therapeutic targets in renal disease. Kidney Int 2001, 60: 14–30.
- 2 Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: Nuclear control of metabolism. Endocr Rev 1999, 20: 649–688.
- 3 Matsuura H, Adachi H, Smart RC, Xu X, Arata J, Jetten AM. Correlation between expression of peroxisome proliferator-activated receptor beta and squamous differentiation in epidermal and tracheo-bronchial epithelial cells. Mol Cell Endocrinol 1999, 147: 85–92.
- 4 Mano H, Kimura C, Fujisawa Y, Kameda T, Watanabe-Mano M, Kaneko H, Kaneda T et al. Cloning and function of rabbit peroxisome proliferator-activated receptor delta/beta in mature osteoclasts. J Biol Chem 2000, 275: 8126–8132.
- 5 Lim H, Paria BC, Das SK, Dinchuk JE, Langenbach R, Trzaskos JM, Dey SK. Multiple female reproductive failures in cyclooxygenase 2-deficient mice. Cell 1997, 91: 197–208.
- 6 Ding NZ, Teng CB, Ma H, Ni H, Ma XH, Xu LB, Yang ZM. Peroxisome proliferator-activated receptor delta expression and regulation in mouse uterus during embryo implantation and decidualization. Mol Reprod Dev 2003, 66: 218–224.
- 7 Barak Y, Liao D, He W, Ong ES, Nelson MC, Olefsky JM, Boland R et al. Effects of peroxisome proliferator-activated receptor delta on placentation, adiposity, and colorectal cancer. Proc Natl Acad Sci USA 2002, 99: 303–308.
- 8 Braissant O, Foufelle F, Scotto C, Dauca M, Wahli W. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology 1996, 137: 354–366.
- 9 Zechel C. The germ cell nuclear factor (GCNF). Mol Reprod Dev 2005, 72: 550–556.
- 10 Chen F, Cooney AJ, Wang Y, Law SW, O'Malley BW. Cloning of a novel orphan receptor (GCNF) expressed during germ cell development. Mol Endocrinol 1994, 8: 1434–1444.
- 11 Yan ZH, Medvedev A, Hirose T, Gotoh H, Jetten AM. Characterization of the response element and DNA binding properties of the nuclear orphan receptor germ cell nuclear factor/retinoid receptor-related testis-associated receptor. J Biol Chem 1997, 272: 10565–10572.
- 12 Cooney AJ, Hummelke GC, Herman T, Chen F, Jackson KJ. Germ cell nuclear factor is a response element-specific repressor of transcription. Biochem Biophys Res Commun 1998, 245: 94–100.
- 13 Borgmeyer U. Dimeric binding of the mouse germ cell nuclear factor. Eur J Biochem 1997, 244: 120–127.
- 14
Hummelke GC,
Meistrich. ML,
Cooney AJ.
Mouse protamine genes are candidate targets for the novel orphan nuclear receptor, germ cell nuclear factor.
Mol Reprod Dev
1998, 50: 396–405.
10.1002/(SICI)1098-2795(199808)50:4<396::AID-MRD3>3.0.CO;2-D CAS PubMed Web of Science® Google Scholar
- 15 Yan Z, Jetten AM. Characterization of the repressor function of the nuclear orphan receptor retinoid receptor-related testis-associated receptor/germ cell nuclear factor. J Biol Chem 2000, 275: 35077–35085.
- 16 Horlein AJ, Naar AM, Heinzel T, Torchia J, Gloss B, Kurokawa R, Ryan A et al. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature 1995, 377: 397–404.
- 17 Chen JD, Evans RM. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature 1995, 377: 454–457.
- 18 Susens U, Aguiluz JB, Evans RM, Borgmeyer U. The germ cell nuclear factor mGCNF is expressed in the developing nervous system. Dev Neurosci 1997, 19: 410–420.
- 19 Chung AC, Cooney AJ. Germ cell nuclear factor. Int J Biochem Cell Biol 2001, 33: 1141–1146.
- 20 Greschik H, Schule R. Germ cell nuclear factor: an orphan receptor with unexpected properties. J Mol Med 1998, 76: 800–810.
- 21 Katz D, Niederberger C, Slaughter GR, Cooney AJ. Characterization of germ cell-specific expression of the orphan nuclear receptor, germ cell nuclear factor. Endocrinology 1997, 138: 4364–4372.
- 22 He CQ, Li CC, Wu YH, An LG, Li YL. Cloning and analyzing the promoter of PPARd. Progress Biochem Biophys 2007, 34: 412–417.
- 23 Benson GV, Lim H, Paria BC, Satokata I, Dey SK, Maas RL. Mechanisms of reduced fertility in Hoxa-10 mutant mice: uterine homeosis and loss of maternal Hoxa-10 expression. Development 1996, 122: 2687–2696.
- 24 Dignam JD, Lebovitz RM, Roeder RG. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res 1983, 11: 1475–1489.
- 25 Yang G, Zhang YL, Buchold GM, Jetten AM, O'Brien DA. Analysis of germ cell nuclear factor transcripts and protein expression during spermatogenesis. Biol Reprod 2003, 68: 1620–1630.
- 26 Govin J, Caron C, Lestrat C, Rousseaux S, Khochbin S. The role of histones in chromatin remodelling during mammalian spermiogenesis. Eur J Biochem 2004, 271: 3459–3469.
- 27 Hummelke GC, Cooney AJ. Reciprocal regulation of the mouse protamine genes by the orphan nuclear receptor germ cell nuclear factor and CREMtau. Mol Reprod Dev 2004, 68: 394–407.
- 28 Blendy JA, Kaestner KH, Schmid W, Gass P, Schutz G. Targeting of the CREB gene leads to up-regulation of a novel CREB mRNA isoform. EMBO J 1996, 15: 1098–1106.
- 29 Rajkovic M, Middendorff R, Wetzel MG., Frkovic D, Damerow S, Seitz HJ, Weitzel JM. Germ cell nuclear factor relieves cAMP-response element modulator tau-mediated activation of the testis-specific promoter of human mitochondrial glycerol-3-phosphate dehydrogenase. J Biol Chem 2004, 279: 52493–52499.
- 30 Valentin M, Balvers M, Pusch W, Weinbauer GF, Knudsen J, Ivell R. Structure and expression of the mouse gene encoding the endozepine-like peptide from haploid male germ cells. Eur J Biochem 2000, 267: 5438–5449.
- 31 Elbrecht A, Chen Y, Cullinan CA, Hayes N, Leibowitz M, Moller DE, Berger J. Molecular cloning, expression and characterization of human peroxisome proliferator activated receptors gamma 1 and gamma 2. Biochem Biophys Res Commun 1996, 224: 431–437.
- 32 Bhattacharya N, Dufour JM, Vo MN, Okita J, Okita R, Kim KH. Differential effects of phthalates on the testis and the liver. Biol Reprod 2005, 72: 745–754.
- 33 Peters JM, Rusyn I, Rose ML, Gonzalez FJ, Thurman RG. Peroxisome proliferator-activated receptor alpha is restricted to hepatic parenchymal cells, not Kupffer cells: implications for the mechanism of action of peroxisome proliferators in hepatocarcinogenesis. Carcinogenesis 2000, 21: 823–826.
- 34 Kliewer SA, Forman BM, Blumberg B, Ong ES, Borgmeyer U, Mangelsdorf DJ, Umesono K et al. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc Natl Acad Sci USA 1994, 91: 7355–7359.