Poster The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2013

Characterisation of DNA methyltransferase (DNMT) genes in a marsupial, the tammar wallaby. (#219)

Danielle Hickford 1 , Marilyn B Renfree 1 , Geoff Shaw 1
  1. Zoology Department, The University of Melbourne, Victoria, Australia
Genomic imprinting describes the parent-of origin-dependent expression of an allele from one but not both chromosomes. Genomic imprinting has been associated with viviparity and placentation and is restricted to therian mammals. In contrast to most eutherians, marsupials have a relatively short gestation which results in an altricial young, which completes its development after a lengthy lactation phase. Thus, marsupials are valuable models for studying the evolution of imprinting mechanisms and controls.

One of the main mechanisms by which genes are imprinted is by DNA methylation, a heritable epigenetic modification resulting from the transfer of a methyl group to the C-5 position of cytosines located within CpG dinucleotides. This epigenetic modification usually results in transcriptional repression and is catalysed by DNA methyltransferases (DNMT). DNMT3a and DNMT3b are de novo methyltransferases responsible for establishing new methylation patterns, whereas DNMT1 maintains existing methylation patterns during cell division. DNMT3L has no catalytic activity but is essential for methylation in the germ line, where it acts as a cofactor to DNMT3a.

The DNMT-1, -3a, -3b and -3L gene families in eutherians are large and contain many alternate transcripts resulting from either alternate promoter usage (DNMT1, -3A, 3L) or differential splicing (all genes). The different promoters result in tissue- or stage-specific Dnmt expression, and alternate splicing of the Dnmt genes can result in transcripts which are translated but lack the catalytic domain- these isoforms may instead act as negative DNMT regulators. Dnmt promoters and splice variants have been well characterised only in the mouse. Marsupials and eutherians diverged from each other more than 160 million years ago, so characterising marsupial DNMT genes and the mechanisms that control them will help elucidate the evolution of these gene families which are involved in the critical task of establishing epigenetic marks.