Extra-embryonic-specific imprinted expression is restricted to defined lineages in the post-implantation embryo

Abstract

A subset of imprinted genes in the mouse have been reported to show imprinted expression that is restricted to the placenta, a short-lived extra-embryonic organ. Notably these so-called 'placental-specific' imprinted genes are expressed from both parental alleles in embryo and adult tissues. The placenta is an embryonic-derived organ that is closely associated with maternal tissue and as a consequence, maternal contamination can be mistaken for maternal-specific imprinted expression. The complexity of the placenta, which arises from multiple embryonic lineages, poses additional problems in accurately assessing allele-specific repressive epigenetic modifications in genes that also show lineage-specific silencing in this organ. These problems require that extra evidence be obtained to support the imprinted status of genes whose imprinted expression is restricted to the placenta. We show here that the extra-embryonic visceral yolk sac (VYS), a nutritive membrane surrounding the developing embryo, shows a similar 'extra-embryonic-lineage-specific' pattern of imprinted expression. We present an improved enzymatic technique for separating the bilaminar VYS and show that this pattern of imprinted expression is restricted to the endoderm layer. Finally, we show that VYS 'extra-embryonic-lineage-specific' imprinted expression is regulated by DNA methylation in a similar manner as shown for genes showing multi-lineage imprinted expression in extra-embryonic, embryonic and adult tissues. These results show that the VYS is an improved model for studying the epigenetic mechanisms regulating extra-embryonic-lineage-specific imprinted expression.

Imprinted genes in mouse placental development and the regulation of fetal energy stores

“…Slc22a3 is expressed exclusively in a subset of cells of the labyrinth layer , Zwart et al 2001a, whereas Slc22a2 expression is restricted to the visceral yolk sac (Hudson et al 2011) and is not expressed in the placenta as previously reported (Zwart et al 2001a). Slc22a3 null mice are viable and fertile with no overt placental defect (Zwart et al 2001b, Jonker et al 2003.…”

Macro lncRNAs

“…The non-overlapped genes Slc22a2 and Slc22a3 in contrast to Igf2r, show restricted imprinted expression only in extra-embryonic tissues such as placenta and visceral yolk sac (VYS). 38,39 Deletion of the Airn promoter resulted in a loss of imprinted expression in this cluster and Igf2r, Slc22a2 and Slc22a3 show bi-allelic expression. 40 To discriminate whether the promoter or Airn expression leads to repression of these proteincoding genes, a polyadenylation cassette was inserted 3 kb downstream from the Airn transcript start site.…”

“…42,44 Recent studies however, challenge the imprinted status of Tssc4, Nap1l4 and Osbpl5, since their high expression in the maternal decidua invalidates their analysis in mouse placenta. 39,45,46 The Nespas macro lncRNA silences the Gnas imprinted gene cluster. The Gnas imprinted gene cluster on mouse chromosome 2 (human chromosome 20) spans a ~100 kb region that contains the two maternally expressed protein-coding Gnas isoforms Nesp and Gnas.…”

Genomic Imprinting and Epigenetic Control of Development

“…In addition, many more genes are imprinted in a tissue-specific manner, for example in certain cell types of the placenta (Hudson et al 2010(Hudson et al , 2011) and brain (Gregg et al 2010a,b). Studies of imprinted genes have identified several common characteristics.…”

“…In addition to genes that are imprinted in all tissues, many more show tissue-specific imprinting, especially in the mouse placenta and brain (Gregg et al 2010a,b;Hudson et al 2010Hudson et al , 2011. Engineered mutations that cause both loss of activity (through targeted deletions) and overexpression (through loss of imprinting) have revealed significant effects on placental function and development, as well as on postnatal and adult behavior (Davies et al 2007;Frost and Moore 2010).…”