Transgenerational epigenetic inheritance has been defined by the study of relatively few loci. We examined a population of recombinant inbred lines with epigenetically mosaic chromosomes consisting of wild-type and CG methylation-depleted segments (epiRILs). Surprisingly, transposons that were immobile in the parental lines displayed stochastic movement in 28% of the epiRILs. Although analysis after eight generations of inbreeding, supported by genome-wide DNA methylation profiling, identified recombined parental chromosomal segments, these were interspersed with unexpectedly high frequencies of nonparental methylation polymorphism. Hence, epigenetic inheritance in hybrids derived from parents with divergent epigenomes permits long-lasting epi-allelic interactions that violate Mendelian expectations. Such persistently ''unstable'' epigenetic states complicate linkage-based epigenomic mapping. Thus, future epigenomic analyses should consider possible genetic instabilities and alternative mapping strategies. The term ''epigenome'' refers to the genome-wide distribution of epigenetic marks such as DNA methylation, histone modifications, and the presence of histone variants (Jenuwein 2002). Specific combinations of these marks are thought to determine the local chromatin structure that affects transcription and genome stability (Jenuwein 2002). In plants and mammals, DNA methylation is the beststudied epigenetic modification. Its faithful propagation is not only critical for proper development but also silences transposable elements (Finnegan 1996;Miura et al. 2001;Singer et al. 2001;Kato et al. 2003;Chan et al. 2005). Thus, apart from a role in development, DNA methylation protects genome integrity.Methylation modifies cytosines preceding guanines ( m CG) and in plants METHYLTRANSFERASE 1 (MET1), a homolog of the mammalian Dnmt1, is required for propagating m CG patterns during DNA replication (Finnegan 1996). Loss of MET1 leads to almost a complete erasure of CG methylation and indirect losses of plantspecific non-CG methylation . Loss of MET1 also results in the suppression of DNA demethylation activities, altered RNA directed de novo methylation, and the redistribution of other repressive marks such as histone H3 dimethylation in Lys 9 and trimethylation in Lys 27 (Soppe et al. 2002;Tariq et al. 2003;Mathieu et al. 2005Mathieu et al. , 2007, creating further epigenetic variation. Thus, transgenerational inheritance of the epigenome in plants is coordinated by the faithful replication of m CG patterns (Mathieu et al. 2007). Notably, loss of m CG results in hypomethylated epi-alleles that, at some loci, may be stably inherited over many generations (Kakutani et al. 1996;Mathieu et al. 2007;Vaughn et al. 2007). This is similar to inheritance of epigenetic states of ribosomal DNA following intercrossed Arabidopsis accessions Richards 2002, 2005;Woo and Richards 2008
Expression data contribute significantly to the biological value of the sequenced human genome,providing extensive information about gene structure and the pattern of gene expression. ESTs,together with SAGE libraries and microarray experiment information,provide a broad and rich view of the transcriptome. However, it is difficult to perform large-scale expression mining of the data generated by these diverse experimental approaches. Not only is the data stored in disparate locations,but there is frequent ambiguity in the meaning of terms used to describe the source of the material used in the experiment. Untangling semantic differences between the data provided by different resources is therefore largely reliant on the domain knowledge of a human expert. We present here eVOC,a system which associates labelled target cDNAs for microarray experiments,or cDNA libraries and their associated transcripts with controlled terms in a set of hierarchical vocabularies. eVOC consists of four orthogonal controlled vocabularies suitable for describing the domains of human gene expression data including Anatomical System,Cell Type,Pathology and Developmental Stage. We have curated and annotated 7016 cDNA libraries represented in dbEST,as well as 104 SAGE libraries,with expression information,and provide this as an integrated,public resource that allows the linking of transcripts and libraries with expression terms. Both the vocabularies and the vocabulary-annotated libraries can be retrieved from http://www.sanbi.ac.za/evoc/. Several groups are involved in developing this resource with the aim of unifying transcript expression information
Massively parallel signature sequencing (MPSS) generates millions of short sequence tags corresponding to transcripts from a single RNA preparation. Most MPSS tags can be unambiguously assigned to genes, thereby generating a comprehensive expression profile of the tissue of origin. From the comparison of MPSS data from 32 normal human tissues, we identified 1,056 genes that are predominantly expressed in the testis. Further evaluation by using MPSS tags from cancer cell lines and EST data from a wide variety of tumors identified 202 of these genes as candidates for encoding cancer͞testis (CT) antigens. Of these genes, the expression in normal tissues was assessed by RT-PCR in a subset of 166 introncontaining genes, and those with confirmed testis-predominant expression were further evaluated for their expression in 21 cancer cell lines. Thus, 20 CT or CT-like genes were identified, with several exhibiting expression in five or more of the cancer cell lines examined. One of these genes is a member of a CT gene family that we designated as CT45. The CT45 family comprises six highly similar (>98% cDNA identity) genes that are clustered in tandem within a 125-kb region on Xq26.3. CT45 was found to be frequently expressed in both cancer cell lines and lung cancer specimens. Thus, MPSS analysis has resulted in a significant extension of our knowledge of CT antigens, leading to the discovery of a distinctive X-linked CT-antigen gene family.germ line ͉ human ͉ transcript
We have addressed the possible epigenetic contribution to heterosis using epigenetic inbred lines (epiRILs) with varying levels and distributions of DNA methylation. One line consistently displayed parent-of-origin heterosis for growth-related traits. Genome-wide transcription profiling followed by a candidate gene approach revealed 33 genes with altered regulation in crosses of this line that could contribute to the observed heterosis. Although none of the candidate genes could explain hybrid vigour, we detected intriguing, hybrid-specific transcriptional regulation of the RPP5 gene, encoding a growth suppressor. RPP5 displayed intermediate transcript levels in heterotic hybrids; surprisingly however, with global loss of fitness of their F2 progeny, we observed striking under-representation of the hybrid-like intermediate levels. Thus, in addition to genetic factors contributing to heterosis, our results strongly suggest that epigenetic diversity and epigenetic regulation of transcription play a role in hybrid vigour and inbreeding depression, and also in the absence of parental genetic diversity.
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