E-Poster Presentation ESA-SRB-ANZBMS 2021

TH/INS: A possible marsupial-specific imprinted domain (#511)

Jooa Kwon 1 , Teruhito Ishihara 1 , Jane C Fenelon 1 , Trent Newman 1 , Geoff Shaw 1 , Marilyn B Renfree 1
  1. School of BioSciences, The University of Melbourne, Parkville, VIC, Australia

Genomic imprinting causes the expression of some genes in a parent-of-origin-specific manner. Comparing the imprinting mechanisms of control between eutherians and marsupials is essential to understand the evolution of imprinting in mammals. More than 80% of eutherian imprinted genes are present as imprinted clusters, allowing genes to share common regulatory elements such as differentially methylated regions (DMRs). In the mouse, an important imprinted domain, the Igf2/H19 locus, incorporating the insulin-like growth factor 2 (Igf2) and the long non-coding RNA, H19, is well characterised in the mouse. It is thought that a neighbouring imprinted gene, Insulin 2 (Ins2) is also regulated by this common DMR in the Igf2/H19 flanking region. In marsupials, the IGF2/H19 imprinted domain is conserved, and Insulin (INS) is also imprinted. However, our laboratory previously found a marsupial-specific gene, TH-INS, that shares exons of tyrosine hydroxylase (TH) and INS in the tammar wallaby Macropus eugenii [1-2]. The methylation pattern at the TH-INS transcription start site (TSS) showed monoallelic expression in tammar pouch young (PY) liver, suggesting it may be a DMR. To confirm this, we first identified a diagnostic single nucleotide polymorphism (SNP) in regions adjacent to the TSS of TH-INS.  We then tested twelve matched maternal and PY samples and found one homozygous mother with a heterozygous PY. Using these samples we confirmed the presence of DNA methylation at the maternal allele of TH-INS TSS in PY liver. We are now investigating the methylation status of the paternal allele. Since the gene shows monoallelic expression in the PY liver we predict that this gene is maternally-imprinted. The proximity of this potential DMR to both TH-INS and INS suggests that the TH/INS region may have evolved as a marsupial-specific imprinted domain.

  1. Stringer JM, Suzuki S, Pask AJ, Shaw G, Renfree MB (2012) Selected imprinting of INS in the marsupial. Epigenetics Chromatin 5:14.
  2. Stringer JM, Pask AJ, Shaw G, Renfree MB (2014) Post-natal imprinting: evidence from marsupials. Heredity (Edinb) 113:145-155.