Lack of reciprocal genomic imprinting of sense and antisense RNA of mouse insulin-like growth factor II receptor in the central nervous system

• Published in: Biochemical and biophysical research communications 1999-04, Vol.257 (2), p.604-608
• Main Authors: Hu, J F, Balaguru, K A, Ivaturi, R D, Oruganti, H, Li, T, Nguyen, B T, Vu, T H, Hoffman, A R
• Format: Article
• Language: English
• Subjects: Alleles; Animals; Animals, Newborn; Binding, Competitive; Central Nervous System - embryology; Central Nervous System - metabolism; DNA Methylation; Female; Gene Expression Regulation, Developmental; Genomic Imprinting - genetics; Male; Mice; Mice, Inbred Strains; Mice, Transgenic; Models, Genetic; Organ Specificity; Polymorphism, Genetic; Promoter Regions, Genetic - genetics; Receptor, IGF Type 2 - genetics; RNA, Antisense - genetics
• ISSN: 0006-291X
• DOI: 10.1006/bbrc.1999.0380

Two models have been proposed to account for the molecular mechanism underlying genomic imprinting of the insulin-like growth factor II receptor gene (Igf2r): expression-competition and promoter DNA methylation. To examine which model best explains the regulation of Igf2r imprinting, we examined the allelic expression of endogenous Igf2r sense and antisense RNAs in mice. In peripheral tissues, Igf2r sense and antisense RNAs show a reciprocal pattern of imprinting and DNA methylation between the two parental alleles: the sense RNA is monoallelically expressed only from the maternal promoter which is unmethylated in region 1, and the antisense RNA is derived solely from the paternal promoter which is unmethylated in region 2. The paternal promoter of sense Igf2r and the maternal promoter of antisense Igf2r are hypermethylated and are transcriptionally suppressed. In CNS, the genomic imprinting of Igf2r sense and antisense RNAs is uncoupled: both parental promoters of Igf2r gene coding for sense RNA are unmethylated and are biallelically used for transcription. In contrast, antisense RNA of Igf2r is derived only from the paternal allele that is unmethylated in region 2, while the methylated maternal allele is silent. Uncoupling of genomic imprinting of Igf2r sense and antisense RNAs in CNS correlates with DNA methylation of the appropriate promoter region, thus favoring the model of DNA methylation over that of antisense as the chief regulator of Igf2r genomic imprinting.