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.