A novel variant of Inpp5f is imprinted in brain, and its expression is correlated with differential methylation of an internal CpG island.
Using a tissue-specific microarray screen in combination with chromosome anomalies in the mouse, we identified a novel imprinted gene, Inpp5f_v2 on mouse chromosome 7. Characterization of this gene reveals a 3.2-kb transcript that is paternally expressed in the brain. Inpp5f_v2 is a variant of the related 4.7-kb transcript, Inpp5f, an inositol phosphatase gene that is biallelically expressed in the mouse. Inpp5f_v2 uses an alternative transcriptional start site within an intron of Inpp5f and thus has a unique alternative first exon. Whereas other imprinted transcripts have a unique first exon located within intron 1 of a longer transcript variant (such as at the Gnas and WT1 loci), Inpp5f_v2 is the first example of which we are aware in which the alternative first exon of an imprinted gene is embedded in a downstream intron (intron 15) of a transcript variant. The CpG island associated with the non-imprinted Inpp5f gene is hypomethylated on both alleles, a finding consistent with biallelic expression, whereas the CpG island present 5' of Inpp5f_v2 is differentially methylated on the maternal versus paternal alleles consistent with its imprinting status.
Choi
Jonathan D
JD
Department of Medical and Molecular Genetics, Guy's, King's and St. Thomas' School of Medicine, King's College London, 8th Floor, Guy's Tower, London SE1 9RT, United Kingdom.
Underkoffler
Lara A
LA
Wood
Andrew J
AJ
Collins
Joelle N
JN
Williams
Patrick T
PT
Golden
Jeffrey A
JA
Schuster
Eugene F
EF
Loomes
Kathleen M
KM
Oakey
Rebecca J
RJ
D000483:Alleles; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism; D002874:Chromosome Mapping; D002875:Chromosomes; D018899:CpG Islands / Q000235:genetics*; D003433:Crosses, Genetic; D019175:DNA Methylation; D005091:Exons; D015870:Gene Expression; D014644:Genetic Variation; D018392:Genomic Imprinting; D017403:In Situ Hybridization; D000072181:Inositol Polyphosphate 5-Phosphatases; D007438:Introns; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D016297:Mutagenesis, Site-Directed; D020411:Oligonucleotide Array Sequence Analysis; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism*; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases