ESA-SRB-AOTA 2019

Transmission of a long non-coding RNA in sperm is a candidate mechanism for achieving genomic imprinting through the histone-protamine transition in therian mammals. (#11)

Teruhito Ishihara 1 , Oliver W Griffith 1 , Shunsuke Suzuki 2 , Marilyn B Renfree 1
  1. School of BioSciences, The University of Melbourne, Melbourne, VIC, Australia
  2. Agricultural and Life Sciences, Shinshu University, Nagano, Japan

Genomic imprinting is an epigenetic phenomenon that leads to the expression of genes in a parent-of-origin-specific way. In higher vertebrates, it occurs only in therian mammals: marsupials and eutherians. Imprinted genes are usually regulated by differentially methylated regions (DMRs). In the maternally-imprinted gene, Mesoderm Specific Transcript (MEST), there is no DMR in marsupials, but imprinting may instead depend on histone modification(s). In contrast, both mouse and human MEST genes have a distinct DMR. Despite this, inhibition of DNA methylation does not induce Mestexpression from the maternal allele in the mouse, suggesting that there may be a conserved non-DMR mechanism, such as histone modification-based imprinting, that controls imprinting in therian mammals. Interestingly, in mature mouse spermatozoa, this gene locus has a distinct active histone mark in its DMR, although 99% of histones are replaced with protamines during spermatogenesis. To achieve histone modification-based imprinting, males need to transmit specific histone marks to the next generation. Therefore, males must overcome the histone-protamine transition because this process would remove specific histone imprinting during spermatogenesis. At the human MEST gene locus, there is an antisense lncRNA, MESTIT1, which is predominantly expressed in the testis and in mature spermatozoa. Accumulation of lncRNAs such as MESTIT1 in spermatozoa could transmit information to the next generation via the histone-protamine transition to establish histone modification-based imprinting. To test this idea, we investigated whether there was a marsupial lncRNA in the MEST gene locus. We identified a novel lncRNA from adult testes of the tammar wallaby and showed that the transcript was present in mature sperm. These data suggest that this antisense transcript in sperm may be necessary to establish genomic imprinting of the MEST genethrough the histone-protamine transition.