The genome-defence gene Tex19.1 suppresses LINE-1 retrotransposons in the placenta and prevents intra-uterine growth retardation in mice.
DNA methylation plays an important role in suppressing retrotransposon activity in mammalian genomes, yet there are stages of mammalian development where global hypomethylation puts the genome at risk of retrotransposition-mediated genetic instability. Hypomethylated primordial germ cells appear to limit this risk by expressing a cohort of retrotransposon-suppressing genome-defence genes whose silencing depends on promoter DNA methylation. Here, we investigate whether similar mechanisms operate in hypomethylated trophectoderm-derived components of the mammalian placenta to couple expression of genome-defence genes to the potential for retrotransposon activity. We show that the hypomethylated state of the mouse placenta results in activation of only one of the hypomethylation-sensitive germline genome-defence genes: Tex19.1. Tex19.1 appears to play an important role in placenta function as Tex19.1(-/-) mouse embryos exhibit intra-uterine growth retardation and have small placentas due to a reduction in the number of spongiotrophoblast, glycogen trophoblast and sinusoidal trophoblast giant cells. Furthermore, we show that retrotransposon mRNAs are derepressed in Tex19.1(-/-) placentas and that protein encoded by the LINE-1 retrotransposon is upregulated in hypomethylated trophectoderm-derived cells that normally express Tex19.1. This study suggests that post-transcriptional genome-defence mechanisms are operating in the placenta to protect the hypomethylated cells in this tissue from retrotransposons and suggests that imbalances between retrotransposon activity and genome-defence mechanisms could contribute to placenta dysfunction and disease.
MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Universityof Edinburgh, Crewe Road, Edinburgh, UK.
Judith
J
Reichmann
James P
JP
Reddington
Diana
D
Best
David
D
Read
Rupert
R
Ollinger
Richard R
RR
Meehan
Ian R
IR
Adams
D000818:Animals; D019175:DNA Methylation; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics* / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000166:cytology; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D017422:Sequence Analysis, DNA; D014327:Trophoblasts / Q000378:metabolism; D015854:Up-Regulation
D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C528631:Tex19 protein, mouse