Dr Christian Belton

The parent-of-origin specificity of imprinted gene expression has been selected for during mammalian evolution, and the dosage control it facilitates is essential for development. Parent-of-origin bias for most genes is dependent on differential germline DNA methylation. A subset of parent of origin bias genes in the trophoblast lineage however do not require germline DNA methylation and so are non-canonically imprinted (NCI). Known NCI genes are all proximal to or encompass transcribed ERVK LTR elements which transposed to these loci in the rodent lineage. If these elements have a physiological function dependent on parent-of-origin and if this is distinct from non-imprinted splice-variants remains unknown. We have generated mouse knock-outs for the NCI LTR within the Gab1 locus in addition to the biallelically expressed promoter of the gene. The placental phenotypes of these lines are distinct both from each-other and from knock-outs which abolish all protein coding expression from the locus. Current and future work focuses on whether allele specificity of expression is conferred by LTR insertion and when during development there is selective pressure for maternal allele silencing. My work will shed light on the features of and requirements for the evolution of imprinted genes, whether these are distinct between the different molecular mechanisms of imprinting and the features and requirements for epigenetic resilient loci more generally.