This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hu, J.-F. Articles by Hoffman, A. R. Search for Related Content PubMed PubMed Citation Articles by Hu, J.-F. Articles by Hoffman, A. R.

Tissue-Specific Imprinting of the Mouse Insulin-Like Growth Factor II Receptor Gene Correlates with Differential Allele-Specific DNA Methylation

Geriatric Research, Educational and Clinical Center and Medical Service Veterans Affairs Palo Alto Health Care System and Division of Endocrinology Department of Medicine Stanford University Palo Alto, California 94304

Imprinted genes may be expressed uniparentally in a tissue- and development-specific manner. The insulin-like growth factor II receptor gene (Igf2r), one of the first imprinted genes to be identified, is an attractive candidate for studying the molecular mechanism of genomic imprinting because it is transcribed monoallelically in the mouse but biallelically in humans. To identify the factors that control genomic imprinting, we examined allelic expression of Igf2r at different ages in interspecific mice. We found that Igf2r is not always monoallelically expressed. Paternal imprinting of Igf2r is maintained in peripheral tissues, including liver, kidney, heart, spleen, intestine, bladder, skin, bone, and skeletal muscle. However, in central nervous system (CNS), Igf2r is expressed from both parental alleles. Southern analysis of the Igf2r promoter (region 1) revealed that, outside of the CNS where Igf2r is monoallelically expressed, the suppressed paternal allele is fully methylated while the expressed maternal allele is completely unmethylated. In CNS, however, both parental alleles are unmethylated in region 1. The importance of DNA methylation in the maintenance of the genomic imprint was also confirmed by the finding that Igf2r imprinting was relaxed by 5-azacytidine treatment. The correlation between genomic imprinting and allelic Igf2r methylation in CNS and other tissues thus suggests that the epigenetic modification in the promoter region may function as one of the major factors in maintaining the monoallelic expression of Igf2r.

This article has been cited by other articles:

				P. B. Samollow The opossum genome: Insights and opportunities from an alternative mammal Genome Res., August 1, 2008; 18(8): 1199 - 1215. [Abstract] [Full Text] [PDF]

				T. L. Wise and D. D. Pravtcheva Delayed Onset of Igf2-Induced Mammary Tumors in Igf2r Transgenic Mice Cancer Res., February 1, 2006; 66(3): 1327 - 1336. [Abstract] [Full Text] [PDF]

				Y. Yamasaki, T. Kayashima, H. Soejima, A. Kinoshita, K.-i. Yoshiura, N. Matsumoto, T. Ohta, T. Urano, H. Masuzaki, T. Ishimaru, et al. Neuron-specific relaxation of Igf2r imprinting is associated with neuron-specific histone modifications and lack of its antisense transcript Air Hum. Mol. Genet., September 1, 2005; 14(17): 2511 - 2520. [Abstract] [Full Text] [PDF]

				C Gicquel, J Weiss, J Amiel, V Gaston, Y Le Bouc, and C D Scott Epigenetic abnormalities of the mannose-6-phosphate/IGF2 receptor gene are uncommon in human overgrowth syndromes J. Med. Genet., January 1, 2004; 41(1): e4 - 4. [Full Text] [PDF]

				Y. Yang, T. Li, T. H. Vu, G. A. Ulaner, J.-F. Hu, and A. R. Hoffman The Histone Code Regulating Expression of the Imprinted Mouse Igf2r Gene Endocrinology, December 1, 2003; 144(12): 5658 - 5670. [Abstract] [Full Text] [PDF]

				J. K. Killian, C. M. Nolan, A. A. Wylie, T. Li, T. H. Vu, A. R. Hoffman, and R. L. Jirtle Divergent evolution in M6P/IGF2R imprinting from the Jurassic to the Quaternary Hum. Mol. Genet., August 1, 2001; 10(17): 1721 - 1728. [Abstract] [Full Text] [PDF]

				A Wutz, H. Theussl, J Dausman, R Jaenisch, D. Barlow, and E. Wagner Non-imprinted Igf2r expression decreases growth and rescues the Tme mutation in mice Development, January 5, 2001; 128(10): 1881 - 1887. [Abstract] [PDF]

				J.-F. Hu, J. Pham, I. Dey, T. Li, T. H. Vu, and A. R. Hoffman Allele-Specific Histone Acetylation Accompanies Genomic Imprinting of the Insulin-Like Growth Factor II Receptor Gene Endocrinology, December 1, 2000; 141(12): 4428 - 4435. [Abstract] [Full Text] [PDF]

				J. Liu, S. Yu, D. Litman, W. Chen, and L. S. Weinstein Identification of a Methylation Imprint Mark within the Mouse Gnas Locus Mol. Cell. Biol., August 15, 2000; 20(16): 5808 - 5817. [Abstract] [Full Text]