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Retrotransposons Regulate Host Genes in Mouse Oocytes and Preimplantation Embryos 127th lab seminar Ho-Su Shin 2004.11.6 Introductions 1. TEs are significant component of eukaryotic genomes, occupying more than one third of mouse and human genome 2. TEs can function as regulatory units for host genes and appear to contribute to many mammlian gene regulatory sequences 3. The effect of TEs whthin their host genome can be viewd as essentially neutral although….. 4. TEs exert a powerful influence on genome evolution Fig.1. Mouse develpmental stages in oocyte&embryo Fig.2. Distribution of 14,813 2-cell library ESTs among six broad categories A.V. Evsikov., et al, 2004 So, they focus in detail on LTR class Ⅲ retrotransposons, which include members of the mammalian apparent LTR retrotransposon(MaLR) and ERV-L families, and investigate the ability of TEs to act as stage specific alternative promoters for a member of host genes Fig. 3. Expression of mobile elements in mouse oocytes and preimplantation embryo A.V. Evsikov., et al, 2004 Results 1. LTR Class III Retrotransposons Are Preferentially Expressed in Full-Grown Oocytes and Cleavage Stage Embryos Abbreviations 1.MT : mouse transcript non autonomous retrotransposon 2.ORR1 : origin region repeat 1 nonautonomous retrotranspospn 3.RLTR1B : subfamily of ERV1 4.IAPEz : intracisternal A – type particle provirus ERV-K family 5.Mor : Morula 6.Bl : Blastocyst LTR classⅢ LTR classⅠ LTR classⅡ 2.Transposable Elements Provide an Alternative 5 Exon Transcripts in Full-Grown Oocytes and Cleavage Stage Embryos 3. Origin of Chimeric Transcripts Chimeric transcripts were missing all exons located upstream of TEs and usually lacked one or more conventional 5’ exons when the TE was located up stream of the gene locus Chimeric transcripts were used to determine (1)whether there was evidence that such transcripts were splice isoforms, as opposed to transcripts arising from an alternative promoter (2) whether such transcripts could be found in other cDNA libraries 4. Conserved LTR splice donor site with Gene AT-rich splice acceptor site characterize MTA LTR – derived chimeric transcript (A) Aligned consensus MaLR LTRs from RepBase compared with a consensus mammalian splice site (B) Alignment of 10 MTAs that contribute 5’ sequence to chimeric transcripts. (C) Orientation bias of MaLR elements within introns. (D) MTA LTRs splice into acceptor sites with a high upstream AT content. 5. MT LTRs and developmental regulation of Chimeric transcript expression Investigation of MTderived chimeric transcripts relative to conventional nonchimeric couterparts They exhibited different patterns of expression 4. MT-Derived SPIN protein in 2-cell stage mouse embryo The predicted N termini of the chimeric and conventional SPIN protein isoforms have scripts might be regulated by another promoter,weused different potential phosphorylation sites suggesting that these two isoforms may function genomic sequence differently. 5. Phylogenetic conservation To approach the question of functional significance from expression MT LTR different angle, class III LTR that contribute to specific chimeric transcripts were assessed for their evolutionary conservation. Trophectoderm (TE) Inner cell Mass( ICM) blastocyst Discussions 1. 2. 3. 4. 5. Different LTR retrotransposons have specific developmentally regulated expression patterns TE-derived chimeric transcripts introduces variation in gene expression and potentially altered gene function either at the RNA or protein level TEs modify gene products and potentially initiate new gene regulatory systems in oocyte and early embryo Oocyte, embryos, and the biology of MaLR Mechanisms of differential TE expression in the oocyte and preimplantation embryo Concluding Remarks Sequential activation and silencing of MaLR and other retrotransposons in oocytes and preimplantation embryos, together with the known links between transposon silencing and chromatin remodeling, lead us to propose that genome remodeling during this period could be initiated and ordered by retrotransposon expression. Concurrent analysis of both transcriptional activaton and epigenetic modifications of specific genomic loci will be required to explore this idea.