This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Liu, J.
Right arrow Articles by Weinstein, L. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liu, J.
Right arrow Articles by Weinstein, L. S.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2000, p. 5808-5817, Vol. 20, No. 16
0270-7306/00/$04.00+0

Identification of a Methylation Imprint Mark within the Mouse Gnas Locus

Jie Liu, Shuhua Yu, Deborah Litman, Weiping Chen, and Lee S. Weinstein*

Metabolic Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892

Received 10 March 2000/Returned for modification 2 May 2000/Accepted 22 May 2000

The imprinted mouse gene Gnas produces the G protein alpha -subunit GSalpha and several other gene products by using alternative promoters and first exons. GSalpha is maternally expressed in some tissues and biallelically expressed in most other tissues, while the gene products NESP55 and XLalpha s are maternally and paternally expressed, respectively. We investigated the mechanisms of Gnas imprinting. The GSalpha promoter and first exon are not methylated on either allele. A further upstream region (approximately from positions -3400 to -939 relative to the GSalpha translational start site) is methylated only on the maternal allele in all adult somatic tissues and in early postimplantation development. Within this region lies a fourth promoter and first exon (exon 1A) that generates paternal-specific mRNAs of unknown function. Exon 1A and GSalpha mRNAs have similar expression patterns, making competition between their promoters unlikely. Differential methylation in this region is established during gametogenesis, being present in oocytes and absent in spermatozoa, and is maintained in preimplantation E3.5d blastocysts. Therefore, this region is a methylation imprint mark. In contrast, differential methylation of the NESP55 and XLalpha s promoter regions (Nesp and Gnasxl) is not established during gametogenesis. The methylation imprint mark that we identified may be important for the tissue-specific imprinting of GSalpha .

* Corresponding author. Mailing address: Metabolic Diseases Branch, NIDDK/NIH, Bldg. 10, Rm. 8C101, Bethesda, MD 20892-1752. Phone: (301) 402-2923. Fax: (301) 402-0374. E-mail: leew{at}amb.niddk.nih.gov.

Molecular and Cellular Biology, August 2000, p. 5808-5817, Vol. 20, No. 16
0270-7306/00/$04.00+0


This article has been cited by other articles:

  • Koerner, M. V., Pauler, F. M., Huang, R., Barlow, D. P. (2009). The function of non-coding RNAs in genomic imprinting. Development 136: 1771-1783 [Abstract] [Full Text]  
  • Chotalia, M., Smallwood, S. A., Ruf, N., Dawson, C., Lucifero, D., Frontera, M., James, K., Dean, W., Kelsey, G. (2009). Transcription is required for establishment of germline methylation marks at imprinted genes. Genes Dev. 23: 105-117 [Abstract] [Full Text]  
  • Weinhaeusel, A., Thiele, S., Hofner, M., Hiort, O., Noehammer, C. (2008). PCR-Based Analysis of Differentially Methylated Regions of GNAS Enables Convenient Diagnostic Testing of Pseudohypoparathyroidism Type Ib. Clin. Chem. 54: 1537-1545 [Abstract] [Full Text]  
  • Krechowec, S., Plagge, A. (2008). Physiological Dysfunctions Associated with Mutations of the Imprinted Gnas Locus. Physiology 23: 221-229 [Abstract] [Full Text]  
  • Xie, T., Chen, M., Gavrilova, O., Lai, E. W., Liu, J., Weinstein, L. S. (2008). Severe Obesity and Insulin Resistance due to Deletion of the Maternal Gs{alpha} Allele Is Reversed by Paternal Deletion of the Gs{alpha} Imprint Control Region. Endocrinology 149: 2443-2450 [Abstract] [Full Text]  
  • Plagge, A., Kelsey, G., Germain-Lee, E. L (2008). Physiological functions of the imprinted Gnas locus and its protein variants G{alpha}s and XL{alpha}s in human and mouse. J Endocrinol 196: 193-214 [Abstract] [Full Text]  
  • Frohlich, L. F., Bastepe, M., Ozturk, D., Abu-Zahra, H., Juppner, H. (2007). Lack of Gnas Epigenetic Changes and Pseudohypoparathyroidism Type Ib in Mice with Targeted Disruption of Syntaxin-16. Endocrinology 148: 2925-2935 [Abstract] [Full Text]  
  • Nikolettos, N., Asimakopoulos, B., Papastefanou, I. S. (2006). Intracytoplasmic Sperm Injection-An Assisted Reproduction Technique That Should Make Us Cautious About Imprinting Deregulation. Reproductive Sciences 13: 317-328 [Abstract]  
  • Van den Veyver, I.B., Al-Hussaini, T.K. (2006). Biparental hydatidiform moles: a maternal effect mutation affecting imprinting in the offspring. Hum Reprod Update 12: 233-242 [Abstract] [Full Text]  
  • Arnaud, P., Hata, K., Kaneda, M., Li, E., Sasaki, H., Feil, R., Kelsey, G. (2006). Stochastic imprinting in the progeny of Dnmt3L-/- females. Hum Mol Genet 15: 589-598 [Abstract] [Full Text]  
  • Tufarelli, C. (2006). The silence RNA keeps: cis mechanisms of RNA mediated epigenetic silencing in mammals. Phil Trans R Soc B 361: 67-79 [Abstract] [Full Text]  
  • Bastepe, M., Juppner, H. (2005). Pseudohypoparathyroidism, Gs{alpha}, and the GNAS Locus. IBMS BoneKEy 2: 20-32 [Full Text]  
  • Germain-Lee, E. L., Schwindinger, W., Crane, J. L., Zewdu, R., Zweifel, L. S., Wand, G., Huso, D. L., Saji, M., Ringel, M. D., Levine, M. A. (2005). A Mouse Model of Albright Hereditary Osteodystrophy Generated by Targeted Disruption of Exon 1 of the Gnas Gene. Endocrinology 146: 4697-4709 [Abstract] [Full Text]  
  • Wettschureck, N., Offermanns, S. (2005). Mammalian G Proteins and Their Cell Type Specific Functions. Physiol. Rev. 85: 1159-1204 [Abstract] [Full Text]  
  • Choi, J. D., Underkoffler, L. A., Wood, A. J., Collins, J. N., Williams, P. T., Golden, J. A., Schuster, E. F. Jr., Loomes, K. M., Oakey, R. J. (2005). A Novel Variant of Inpp5f Is Imprinted in Brain, and Its Expression Is Correlated with Differential Methylation of an Internal CpG Island. Mol. Cell. Biol. 25: 5514-5522 [Abstract] [Full Text]  
  • Chen, M., Gavrilova, O., Liu, J., Xie, T., Deng, C., Nguyen, A. T., Nackers, L. M., Lorenzo, J., Shen, L., Weinstein, L. S. (2005). Alternative Gnas gene products have opposite effects on glucose and lipid metabolism. Proc. Natl. Acad. Sci. USA 102: 7386-7391 [Abstract] [Full Text]  
  • Plagge, A., Isles, A. R., Gordon, E., Humby, T., Dean, W., Gritsch, S., Fischer-Colbrie, R., Wilkinson, L. S., Kelsey, G. (2005). Imprinted Nesp55 Influences Behavioral Reactivity to Novel Environments. Mol. Cell. Biol. 25: 3019-3026 [Abstract] [Full Text]  
  • O'Neill, M. J. (2005). The influence of non-coding RNAs on allele-specific gene expression in mammals. Hum Mol Genet 14: R113-R120 [Abstract] [Full Text]  
  • Liu, J., Chen, M., Deng, C., Bourc'his, D., Nealon, J. G., Erlichman, B., Bestor, T. H., Weinstein, L. S. (2005). From the Cover: Identification of the control region for tissue-specific imprinting of the stimulatory G protein {alpha}-subunit. Proc. Natl. Acad. Sci. USA 102: 5513-5518 [Abstract] [Full Text]  
  • Liu, J., Nealon, J. G., Weinstein, L. S. (2005). Distinct patterns of abnormal GNAS imprinting in familial and sporadic pseudohypoparathyroidism type IB. Hum Mol Genet 14: 95-102 [Abstract] [Full Text]  
  • Mantovani, G., Bondioni, S., Locatelli, M., Pedroni, C., Lania, A. G., Ferrante, E., Filopanti, M., Beck-Peccoz, P., Spada, A. (2004). Biallelic Expression of the Gs{alpha} Gene in Human Bone and Adipose Tissue. J. Clin. Endocrinol. Metab. 89: 6316-6319 [Abstract] [Full Text]  
  • Weinstein, L. S., Liu, J., Sakamoto, A., Xie, T., Chen, M. (2004). Minireview: GNAS: Normal and Abnormal Functions. Endocrinology 145: 5459-5464 [Abstract] [Full Text]  
  • Chen, M., Haluzik, M., Wolf, N. J., Lorenzo, J., Dietz, K. R., Reitman, M. L., Weinstein, L. S. (2004). Increased Insulin Sensitivity in Paternal Gnas Knockout Mice Is Associated with Increased Lipid Clearance. Endocrinology 145: 4094-4102 [Abstract] [Full Text]  
  • Mantovani, G., Bondioni, S., Lania, A. G., Corbetta, S., de Sanctis, L., Cappa, M., Di Battista, E., Chanson, P., Beck-Peccoz, P., Spada, A. (2004). Parental Origin of Gs{alpha} Mutations in the McCune-Albright Syndrome and in Isolated Endocrine Tumors. J. Clin. Endocrinol. Metab. 89: 3007-3009 [Abstract] [Full Text]  
  • Sakamoto, A., Liu, J., Greene, A., Chen, M., Weinstein, L. S. (2004). Tissue-specific imprinting of the G protein Gs{alpha} is associated with tissue-specific differences in histone methylation. Hum Mol Genet 13: 819-828 [Abstract] [Full Text]  
  • Li, T., Vu, T. H., Ulaner, G. A., Yang, Y., Hu, J.-F., Hoffman, A. R. (2004). Activating and silencing histone modifications form independent allelic switch regions in the imprinted Gnas gene. Hum Mol Genet 13: 741-750 [Abstract] [Full Text]  
  • Lania, A., Mantovani, G., Spada, A. (2003). Genetics of Pituitary Tumors: Focus on G-Protein Mutations. Exp. Biol. Med. 228: 1004-1017 [Abstract] [Full Text]  
  • Bastepe, M., Juppner, H. (2003). Pseudohypoparathyroidism and Mechanisms of Resistance toward Multiple Hormones: Molecular Evidence to Clinical Presentation. J. Clin. Endocrinol. Metab. 88: 4055-4058 [Full Text]  
  • Mantovani, G., Maghnie, M., Weber, G., De Menis, E., Brunelli, V., Cappa, M., Loli, P., Beck-Peccoz, P., Spada, A. (2003). Growth Hormone-Releasing Hormone Resistance in Pseudohypoparathyroidism Type Ia: New Evidence for Imprinting of the Gs{alpha} Gene. J. Clin. Endocrinol. Metab. 88: 4070-4074 [Abstract] [Full Text]  
  • Liu, J., Erlichman, B., Weinstein, L. S. (2003). The Stimulatory G Protein {alpha}-Subunit Gs{alpha} Is Imprinted in Human Thyroid Glands: Implications for Thyroid Function in Pseudohypoparathyroidism Types 1A and 1B. J. Clin. Endocrinol. Metab. 88: 4336-4341 [Abstract] [Full Text]  
  • Coombes, C., Arnaud, P., Gordon, E., Dean, W., Coar, E. A., Williamson, C. M., Feil, R., Peters, J., Kelsey, G. (2003). Epigenetic Properties and Identification of an Imprint Mark in the Nesp-Gnasxl Domain of the Mouse Gnas Imprinted Locus. Mol. Cell. Biol. 23: 5475-5488 [Abstract] [Full Text]  
  • El-Maarri, O., Seoud, M., Coullin, P., Herbiniaux, U., Oldenburg, J., Rouleau, G., Slim, R. (2003). Maternal alleles acquiring paternal methylation patterns in biparental complete hydatidiform moles. Hum Mol Genet 12: 1405-1413 [Abstract] [Full Text]  
  • Holmes, R., Williamson, C., Peters, J., Denny, P., RIKEN GER Group, , GSL Members, , Wells, C. (2003). A Comprehensive Transcript Map of the Mouse Gnas Imprinted Complex. Genome Res 13: 1410-1415 [Abstract] [Full Text]  
  • Arnaud, P., Monk, D., Hitchins, M., Gordon, E., Dean, W., Beechey, C. V., Peters, J., Craigen, W., Preece, M., Stanier, P., Moore, G. E., Kelsey, G. (2003). Conserved methylation imprints in the human and mouse GRB10 genes with divergent allelic expression suggests differential reading of the same mark. Hum Mol Genet 12: 1005-1019 [Abstract] [Full Text]  
  • Mantovani, G., Ballare, E., Giammona, E., Beck-Peccoz, P., Spada, A. (2002). The Gs{alpha} Gene: Predominant Maternal Origin of Transcription in Human Thyroid Gland and Gonads. J. Clin. Endocrinol. Metab. 87: 4736-4740 [Abstract] [Full Text]  
  • Bastepe, M., Gunes, Y., Perez-Villamil, B., Hunzelman, J., Weinstein, L. S., Juppner, H. (2002). Receptor-Mediated Adenylyl Cyclase Activation Through XL{alpha}s, the Extra-Large Variant of the Stimulatory G Protein {alpha}-Subunit. Mol. Endocrinol. 16: 1912-1919 [Abstract] [Full Text]  
  • Shore, E. M., Ahn, J., de Beur, S. J., Li, M., Xu, M., Gardner, R.J. M., Zasloff, M. A., Whyte, M. P., Levine, M. A., Kaplan, F. S. (2002). Paternally Inherited Inactivating Mutations of the GNAS1 Gene in Progressive Osseous Heteroplasia. NEJM 346: 99-106 [Abstract] [Full Text]  
  • Weinstein, L. S., Yu, S., Warner, D. R., Liu, J. (2001). Endocrine Manifestations of Stimulatory G Protein {alpha}-Subunit Mutations and the Role of Genomic Imprinting. Endocr. Rev. 22: 675-705 [Abstract] [Full Text]  
  • Bastepe, M., Pincus, J. E., Sugimoto, T., Tojo, K., Kanatani, M., Azuma, Y., Kruse, K., Rosenbloom, A. L., Koshiyama, H., Juppner, H. (2001). Positional dissociation between the genetic mutation responsible for pseudohypoparathyroidism type Ib and the associated methylation defect at exon A/B: evidence for a long-range regulatory element within the imprinted GNAS1 locus. Hum Mol Genet 10: 1231-1241 [Abstract] [Full Text]  
  • Vu, T. H., Hoffman, A. R. (2000). Comparative Genomics Sheds Light on Mechanisms of Genomic Imprinting. Genome Res 10: 1660-1663 [Full Text]  
  • Wu, W.-I., Schwindinger, W. F., Aparicio, L. F., Levine, M. A. (2001). Selective Resistance to Parathyroid Hormone Caused by a Novel Uncoupling Mutation in the Carboxyl Terminus of Galpha s. A CAUSE OF PSEUDOHYPOPARATHYROIDISM TYPE Ib. J. Biol. Chem. 276: 165-171 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»