Nucleic Acids Research, 1990, Vol. 18, No. 13 3975-3982
© 1990
MOLECULAR BIOLOGY |
CpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2
Department of Genetics, Harvard Medical School and Department of Molecular Biology, Massachusetts General Hospital Boston, MA, 02114, USA
*To whom correspondence should be addressed at Laboratory of Molecular Neurobiology, Neuroscience Center, Massachusetts General Hospital (East), Charlestown, MA 02129, USA.
Received January 25, 1990. Accepted April 9, 1990.
DNA methylation at Hpall (CmCGG) sites inhibits expression of a human proenkephalin-CAT fusion gene when it is transiently expressed in CV-1 cells or stably expressed in C6-glioma cells. The inhibitory effects of Hpall methylation have been mapped to a site within the human proenkephalin promoter located at position –72 relative to the start site of transcription. This region spans a cAMP and phorbol ester inducible enhancer and methylation at this position inhibits both basal transcription and transcription induced by either cAMP or TPA. The Hpall site is located within an element which binds the transcription factor AP-2. In vitro methylation at this Hpall site inhibits the binding of AP-2. These results suggest that CpG methylation inhibits proenkephalin gene expression by directly interfering with the binding of a positively acting transcription factor previously shown to be essential for maximal basal, cAMP, and TPA inducible transcription.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Aoki, T. Terada, M. Kajiwara, K. Ogasawara, I. Ikai, O. Ogawa, T. Katsura, and K.-i. Inui Kidney-specific expression of human organic cation transporter 2 (OCT2/SLC22A2) is regulated by DNA methylation Am J Physiol Renal Physiol, July 1, 2008; 295(1): F165 - F170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Matouk and P. A. Marsden Epigenetic Regulation of Vascular Endothelial Gene Expression Circ. Res., April 25, 2008; 102(8): 873 - 887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Liu, M. Ballaney, U. Al-alem, C. Quan, X. Jin, F. Perera, L.-C. Chen, and R. L. Miller Combined Inhaled Diesel Exhaust Particles and Allergen Exposure Alter Methylation of T Helper Genes and IgE Production In Vivo Toxicol. Sci., March 1, 2008; 102(1): 76 - 81. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Li, L. Da, H. Tang, T. Li, and M. Zhao CpG methylation plays a vital role in determining tissue- and cell-specific expression of the human cell-death-inducing DFF45-like effector A gene through the regulation of Sp1/Sp3 binding Nucleic Acids Res., January 17, 2008; 36(1): 330 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kitamura, Y. Kabuyama, A. Kamataki, M. K. Homma, H. Kobayashi, S. Aota, S.-i. Kikuchi, and Y. Homma Enhancement of lymphocyte migration and cytokine production by ephrinB1 system in rheumatoid arthritis Am J Physiol Cell Physiol, January 1, 2008; 294(1): C189 - C196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Szyf The Dynamic Epigenome and its Implications in Toxicology Toxicol. Sci., November 1, 2007; 100(1): 7 - 23. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. D'Alessio, I. C. G. Weaver, and M. Szyf Acetylation-Induced Transcription Is Required for Active DNA Demethylation in Methylation-Silenced Genes Mol. Cell. Biol., November 1, 2007; 27(21): 7462 - 7474. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Tomikawa, K. Fukatsu, S. Tanaka, and K. Shiota DNA Methylation-dependent Epigenetic Regulation of Dimethylarginine Dimethylaminohydrolase 2 Gene in Trophoblast Cell Lineage J. Biol. Chem., April 28, 2006; 281(17): 12163 - 12169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. C. G. Weaver, F. A. Champagne, S. E. Brown, S. Dymov, S. Sharma, M. J. Meaney, and M. Szyf Reversal of Maternal Programming of Stress Responses in Adult Offspring through Methyl Supplementation: Altering Epigenetic Marking Later in Life J. Neurosci., November 23, 2005; 25(47): 11045 - 11054. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Ulrey, L. Liu, L. G. Andrews, and T. O. Tollefsbol The impact of metabolism on DNA methylation Hum. Mol. Genet., April 15, 2005; 14(suppl_1): R139 - R147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. Danam, S. R. Howell, T. P. Brent, and L. C. Harris Epigenetic regulation of O6-methylguanine-DNA methyltransferase gene expression by histone acetylation and methyl-CpG binding proteins Mol. Cancer Ther., January 1, 2005; 4(1): 61 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Chan, J. E. Fish, C. D'Abreo, S. Lin, G. B. Robb, A.-M. Teichert, F. Karantzoulis-Fegaras, A. Keightley, B. M. Steer, and P. A. Marsden The Cell-specific Expression of Endothelial Nitric-oxide Synthase: A ROLE FOR DNA METHYLATION J. Biol. Chem., August 13, 2004; 279(33): 35087 - 35100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Milutinovic, S. E. Brown, Q. Zhuang, and M. Szyf DNA Methyltransferase 1 Knock Down Induces Gene Expression by a Mechanism Independent of DNA Methylation and Histone Deacetylation J. Biol. Chem., July 2, 2004; 279(27): 27915 - 27927. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Detich, V. Bovenzi, and M. Szyf Valproate Induces Replication-independent Active DNA Demethylation J. Biol. Chem., July 18, 2003; 278(30): 27586 - 27592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-G. Zhu, K. Srinivasan, Z. Dai, W. Duan, L. J. Druhan, H. Ding, L. Yee, M. A. Villalona-Calero, C. Plass, and G. A. Otterson Methylation of Adjacent CpG Sites Affects Sp1/Sp3 Binding and Activity in the p21Cip1 Promoter Mol. Cell. Biol., June 15, 2003; 23(12): 4056 - 4065. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Lu, A. Wu, D. Ray, C. Deng, J. Attwood, S. Hanash, M. Pipkin, M. Lichtenheld, and B. Richardson DNA Methylation and Chromatin Structure Regulate T Cell Perforin Gene Expression J. Immunol., May 15, 2003; 170(10): 5124 - 5132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Melzner, V. Scott, K. Dorsch, P. Fischer, M. Wabitsch, S. Bruderlein, C. Hasel, and P. Moller Leptin Gene Expression in Human Preadipocytes Is Switched on by Maturation-induced Demethylation of Distinct CpGs in Its Proximal Promoter J. Biol. Chem., November 15, 2002; 277(47): 45420 - 45427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Lu, D. Ray, D. Gutsch, and B. Richardson Effect of DNA methylation and chromatin structure on ITGAL expression Blood, May 29, 2002; 99(12): 4503 - 4508. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Fukushima, N. Sato, T. Ueki, C. Rosty, K. M. Walter, R. E. Wilentz, C. J. Yeo, R. H. Hruban, and M. Goggins Aberrant Methylation of Preproenkephalin and p16 Genes in Pancreatic Intraepithelial Neoplasia and Pancreatic Ductal Adenocarcinoma Am. J. Pathol., May 1, 2002; 160(5): 1573 - 1581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Benjamin and J.-P. Jost Reversal of methylation-mediated repression with short-chain fatty acids: evidence for an additional mechanism to histone deacetylation Nucleic Acids Res., September 1, 2001; 29(17): 3603 - 3610. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Griswold and J.-S. Kim Site-Specific Methylation of the Promoter Alters Deoxyribonucleic Acid-Protein Interactions and Prevents Follicle-Stimulating Hormone Receptor Gene Transcription Biol Reprod, February 1, 2001; 64(2): 602 - 610. [Abstract] [Full Text]
|
|
|
|
 |
|
 Z. Dong, X. Wang, and B. M. Evers Site-specific DNA methylation contributes to neurotensin/neuromedin N expression in colon cancers Am J Physiol Gastrointest Liver Physiol, December 1, 2000; 279(6): G1139 - G1147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Suzuki-Ishigaki, K. Numayama-Tsuruta, A. Kuramasu, E. Sakurai, Y. Makabe, S. Shimura, K. Shirato, K. Igarashi, T. Watanabe, and H. Ohtsu The mouse L-histidine decarboxylase gene: structure and transcriptional regulation by CpG methylation in the promoter region Nucleic Acids Res., July 15, 2000; 28(14): 2627 - 2633. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kinoshita, Y. Shi, C. Sandefur, L. F. Meisner, C. Chang, A. Choon, C. R. Reznikoff, G. S. Bova, A. Friedl, and D. F. Jarrard Methylation of the Androgen Receptor Minimal Promoter Silences Transcription in Human Prostate Cancer Cancer Res., July 1, 2000; 60(13): 3623 - 3630. [Abstract] [Full Text]
|
|
|
|
 |
|
 Q. Dang, J. Auten, and I. Plavec Human Beta Interferon Scaffold Attachment Region Inhibits De Novo Methylation and Confers Long-Term, Copy Number-Dependent Expression to a Retroviral Vector J. Virol., March 15, 2000; 74(6): 2671 - 2678. [Abstract] [Full Text]
|
|
|
|
|
|
B. Santoso, B. D. Ortiz, and A. Winoto Control of Organ-specific Demethylation by an Element of the T-cell Receptor-alpha Locus Control Region J. Biol. Chem., January 21, 2000; 275(3): 1952 - 1958. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Dottori, M. Down, A. Huttmann, D. R. Fitzpatrick, and A. W. Boyd Cloning and Characterization of EphA3 (Hek) Gene Promoter: DNA Methylation Regulates Expression in Hematopoietic Tumor Cells Blood, October 1, 1999; 94(7): 2477 - 2486. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.-Y. Law and H. H. Loh Regulation of Opioid Receptor Activities J. Pharmacol. Exp. Ther., May 1, 1999; 289(2): 607 - 624. [Abstract] [Full Text]
|
|
|
|
|
|
W. B. Archey, M. P. Sweet, G. C. Alig, and B. A. Arrick Methylation of CpGs as a Determinant of Transcriptional Activation at Alternative Promoters for Transforming Growth Factor-{beta}3 Cancer Res., May 1, 1999; 59(10): 2292 - 2296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kuramasu, H. Saito, S. Suzuki, T. Watanabe, and H. Ohtsu Mast Cell-/Basophil-specific Transcriptional Regulation of Human L-Histidine Decarboxylase Gene by CpG Methylation in the Promoter Region J. Biol. Chem., November 20, 1998; 273(47): 31607 - 31614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Hendrich and A. Bird Identification and Characterization of a Family of Mammalian Methyl-CpG Binding Proteins Mol. Cell. Biol., November 1, 1998; 18(11): 6538 - 6547. [Abstract] [Full Text]
|
|
|
|
|
|
S. Kudo Methyl-CpG-Binding Protein MeCP2 Represses Sp1-Activated Transcription of the Human Leukosialin Gene When the Promoter Is Methylated Mol. Cell. Biol., September 1, 1998; 18(9): 5492 - 5499. [Abstract] [Full Text]
|
|
|
|
 |
|
 N. Yokomori, M. Tawata, T. Saito, H. Shimura, and T. Onaya Regulation of the Rat Thyrotropin Receptor Gene by the Methylation-Sensitive Transcription Factor GA-Binding Protein Mol. Endocrinol., August 1, 1998; 12(8): 1241 - 1249. [Abstract] [Full Text]
|
|
|
|
 |
|
 C.P. Clifford and D.J.R. Nunez Human {beta}-myosin heavy chain mRNA prevalence is inversely related to the degree of methylation of regulatory elements Cardiovasc Res, June 1, 1998; 38(3): 736 - 743. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Rountree and E. U. Selker DNA methylation inhibits elongation but not initiation of transcription in Neurospora crassa Genes & Dev., September 15, 1997; 11(18): 2383 - 2395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Feil, M. D. Boyano, N. D. Allen, and G. Kelsey Parental Chromosome-specific Chromatin Conformation in the Imprinted U2af1-rs1 Gene in the Mouse J. Biol. Chem., August 15, 1997; 272(33): 20893 - 20900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zhang, Z.-Q. Chen, Z. Wang, W. Mohan, and S.-P. Tam Protein-DNA Interactions at a Drug-responsive Element of the Human Apolipoprotein A-I Gene J. Biol. Chem., October 25, 1996; 271(43): 27152 - 27160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kudo and M. Fukuda Tissue-specific Transcriptional Regulation of Human Leukosialin (CD43) Gene Is Achieved by DNA Methylation J. Biol. Chem., June 2, 1995; 270(22): 13298 - 13302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sato, D.-M. Xiao, H. Li, F. L. Huang, and K.-P. Huang Structure and Regulation of the Gene Encoding the Neuron-specific Protein Kinase C Substrate Neurogranin (RC3 Protein) J. Biol. Chem., April 28, 1995; 270(17): 10314 - 10322. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G P Pfeifer and A D Riggs Chromatin differences between active and inactive X chromosomes revealed by genomic footprinting of permeabilized cells using DNase I and ligation-mediated PCR. Genes & Dev., June 1, 1991; 5(6): 1102 - 1113. [Abstract] [PDF]
|
|