Differential biallelic activation of three insulin-like growth factor II promoters in the mouse central nervous system.
Imprinting of the insulin-like growth factor II gene (IGF-II) is conserved in human, rat, and mouse. In human liver and chondrocytes, IGF-II transcripts from promoter hP1 are always derived from both parental alleles, while transcripts from promoters hP2-hP4 are from one parental allele. To examine the promoter-specific imprinting pattern of mouse IGF-II, we examined IGF-II expression in F1 generation mice derived from crossing M. spretus with M. musculus using a novel BsaA1 polymorphism in mouse IGF-II exon 6. There was maintenance of maternal IGF-II imprinting in all non-central nervous system (CNS) tissues in the F1 generation animals. However, there was biallelic expression of the IGF-II gene in CNS. Allelic expression of each IGF-II promoter transcript was examined by full-length cDNA amplification with promoter-specific primers. In every tissue in which IGF-II was imprinted, IGF-II transcripts were derived from paternal promoters mP1-mP3, while the maternal allele was suppressed. In the CNS, however, promoters mP1-mP3 of the imprinted maternal allele became activated, leading to the biallelic expression of IGF-II. Moreover, the expression of IGF-II from each parental allele differed in various CNS regions. In leptomeninges, mP1-mP3 drive IGF-II expression predominantly from the paternal allele, while in some CNS regions, the promoter transcripts were primarily from the maternal allele. The coordinate regulation of mouse IGF-II promoters suggests the presence of an upstream imprinting complex controlling IGF-II imprinting.(ABSTRACT TRUNCATED AT 250 WORDS)
Hu
J F
JF
Medical Service, Veterans Affairs Medical Center, Palo Alto, California, USA.
Vu
T H
TH
Hoffman
A R
AR
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002490:Central Nervous System / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010375:Pedigree; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
D007335:Insulin-Like Growth Factor II