The PcG gene Sfmbt2 is paternally expressed in extraembryonic tissues

Abstract

Genomic imprinting has dramatic effects on placental development, as has been clearly observed in interspecific hybrid, somatic cell nuclear transfer, and uniparental embryos. In fact, the earliest defects in uniparental embryos are evident first in the extraembryonic trophoblast. We performed a microarray comparison of gynogenetic and androgenetic mouse blastocysts, which are predisposed to placental pathologies, to identify imprinted genes. In addition to identifying a large number of known imprinted genes, we discovered that the Polycomb group (PcG) gene Sfmbt2 is imprinted. Sfmbt2 is expressed preferentially from the paternal allele in early embryos, and in later stage extraembryonic tissues. A CpG island spanning the transcriptional start site is differentially methylated on the maternal allele in e14.5 placenta. Sfmbt2 is located on proximal chromosome 2, in a region known to be imprinted, but for which no genes had been identified until now. This possibly identifies a new imprinted domain within the murine genome. We further demonstrate that murine SFMBT2 protein interacts with the transcription factor YY1, similar to the Drosophila PHO-RC. KeywordsGenomic Imprinting; Sfmbt2; PcG gene; Extraembryonic tissues; placenta; MMU2; YY1; microarrays; uniparental embryos Results and DiscusssionThe role played by imprinted genes in placental development is gaining wider attention as the impact of imprinting disruptions on placental pathology is explored. Both hyper-and hypoplastic placentation are linked to imprinted gene function (Kanayama et al., 2002;Murdoch et al., 2006; reviewed in Kaneko-Ishino et al., 2003). The most dramatic example of this is diploid, uniparental embryos. Gynogenetic embryos (two maternal/no paternal genomes) and androgenetic embryos (two paternal/no maternal genomes) both exhibit defects in the earliest differentiated tissue in mammals, the extraembryonic trophoblast (Barton et al., 1984;McGrath and Solter, 1984;Mann, 2005). At mid-gestation, gynogenetic embryos possess only a few residual trophoblast giant cells while androgenetic embryos are characterized by a mass of hypertrophic trophoblast. These observations indicate that a suite of genes required * Corresponding author. s.varmuza@utoronto.ca; tel. 1-416-978-2759; FAX 1-416-978-8532. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptGene Expr Patterns. Author manuscript; available in PMC 2009 January 1. Published in final edited form as:Gene Expr Patterns. 2008 January ; 8(2): 107-116. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manu...

Genome-wide impact of a recently expanded microRNA cluster in mouse

“…4A and SI Appendix). These findings are consistent with mRNA expression data for Sfmbt2 (30), which has been shown to be maternally imprinted (and therefore paternally expressed) in the placenta (20). Therefore, it is likely that expression of the intronic miRNA cluster is dependent on transcription of the entire gene, as has been suggested for many miRNAs similarly positioned within host genes (31).…”

“…Inhibition of Lats2 and our other validated target, Dedd2, fits well with the position of the Sfmbt2 cluster in a paternally expressed placental gene (20), because such genes are thought to be commonly involved in redistributing resources from mother to offspring under the parental sex conflict model (41). In this model, the father has an evolutionary incentive to promote fetal growth at the expense of maternal resources as only the fetus shares half of his genetic material.…”

“…Closer inspection of the largest cluster of hits, located proximally on chromosome 2, revealed that they were derived from the 10th intron of Sfmbt2, a polycomb group gene (20). In total, this intron contains 36 distinct miRNAs, which we refer to as the Sfmbt2 cluster miRNAs (Fig.…”

Chromatin regulation: How complex does it get?

“…58,59 The closest vertebrate ortholog of Pho is the transcription factor Yin Yang-1 (YY1). 60 However, although YY1 and SFMBT2 co-immunoprecipitate upon overexpression in mammalian cells, 61 they do not appear to form a stable complex.…”

Using next-generation RNA sequencing to identify imprinted genes

“…To date, about 120 imprinted genes have been identified and successfully validated in humans and mice (Morison et al, 2001(Morison et al, , 2005Prickett and Oakey, 2012), and we know this list is not complete. Genomewide and transcriptome-wide approaches have been applied to detect genomic imprinting (Maeda and Hayashizaki, 2006;Henckel and Arnaud, 2010), including microarray expression profiling of parthenogenote and androgenote embryos (Mizuno et al, 2002;Nikaido et al, 2003;Kuzmin et al, 2008;Sritanaudomchai et al, 2010) and uniparental disomic mice (Choi et al, 2001(Choi et al, , 2005Schulz et al, 2006), expression profiling using allele-specific single-nucleotide polymorphism (SNP) arrays (Pollard et al, 2008;Serre et al, 2008;Brideau et al, 2010;Morcos et al, 2011) and computational prediction methods (Ke et al, 2002;Yang et al, 2003;Luedi et al, 2005Luedi et al, , 2007Brideau et al, 2010). Recently, RNA-seq has become the method of choice for in-depth analysis of the whole transcriptome of an organism (Ozsolak and Milos, 2011).…”