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The expression of two adjacent imprinted genes,  Peg3  and  Zim1 , is inversely correlated: down-regulation of  Peg3  coinciding with up-regulation of  Zim1 . The current study characterized this inverse correlation using a mutant allele targeting  Peg3 . According to the results, the mutation on the paternal allele of  Peg3  resulted in a dramatic increase in the transcription levels of the maternal allele of  Zim1 , suggesting the involvement of unknown  trans  factors in this trans-allelic event. Subsequent ChIP experiments revealed that the protein encoded by  Peg3  itself binds to the zinc finger exon of  Zim1 , which is modified with the repression mark H3K9me3. Interestingly, the levels of H3K9me3 on  Zim1  are also reduced in the mutant cells lacking the protein PEG3, suggesting potential roles for PEG3 in establishing H3K9me3 on  Zim1 . Reintroducing PEG3 into the mutant cell restored down-regulation of  Zim1 , confirming the predicted repressor role for  Peg3  on  Zim1 . Overall, these results demonstrated that paternally expressed  Peg3  controls maternally expressed  Zim1  as a trans factor. The current study also provides the first case for the trans-allelic interaction of two oppositely imprinted genes through their gene products.

Paternally Expressed Peg3 Controls Maternally Expressed Zim1 as a Trans Factor