DNA methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patientsThe first genome-scale DNA methylation study on pancreatic islets from type 2 diabetic patients identifies disease-associated DNA methylation pattern that translate into aberrant gene expression in novel factors relevant for β-cell function and survival.

RNA editing in mitochondria and chloroplasts of land plants alters transcript sequences by site-specific conversions of cytidines into uridines. RNA editing frequencies vary extremely between land plant clades, ranging from zero in some liverworts to more than 2,000 sites in lycophytes. Unique pentatricopeptide repeat (PPR) proteins with variable domain extension (E/E+/DYW) have recently been identified as specific editing site recognition factors in model plants. The distinctive functions of these PPR protein domain additions have remained unclear, although deaminase function has been proposed for the DYW domain. To shed light on diversity of RNA editing and DYW proteins at the origin of land plant evolution, we investigated editing patterns of the mitochondrial nad5, nad4, and nad2 genes in a wide sampling of more than 100 liverworts and mosses using the recently developed PREPACT program (www.prepact.de) and exemplarily confirmed predicted RNA editing sites in selected taxa. Extreme variability in RNA editing frequency is seen both in liverworts and mosses. Only few editings exist in the liverwort Lejeunea cavifolia or the moss Pogonatum urnigerum whereas up to 20% of cytidines are edited in the liverwort Haplomitrium mnioides or the moss Takakia lepidozioides. Interestingly, the latter are taxa that branch very early within their respective clades. Amplicons targeting the E/E+/DYW domains and subsequent random clone sequencing show DYW domains among bryophytes to be highly conserved in comparison with their angiosperm counterparts and to correlate well with RNA editing frequencies regarding their diversities. We propose that DYW proteins are the key players of RNA editing at the origin of land plants.

Transcripts in mitochondria and chloroplasts of land plants are modified through RNA editing, the exchanges of pyrimidines-a post-transcriptional process that may affect more than 1,000 sites in the mitochondrial transcriptomes of some plant species. RNA editing mainly acts as a correcting mechanism to re-create evolutionary conserved coding sequences on mRNA level and can be reasonably well predicted in new plant organelle gene sequence data. Identification and annotation of RNA editing sites is cumbersome and error-prone for larger data sets or organelle sequences subject to highly frequent RNA editing. We here present PREPACT, WWW-accessible at http://www.prepact.de , which allows prediction, analysis, annotation and graphical display of RNA editing sites for both directions of pyrimidine exchanges, using the recently proposed RNA editing nomenclature. PREPACT offers prediction of RNA editing, analysis of partial editing in cDNA pools and a BLASTX mode for simultaneous prediction of genes and RNA editing sites in novel sequences. Output options include (i) lists and annotations of RNA editing sites, (ii) sequence alignments with user-controlled color highlighting of editings, (iii) graphical displays of RNA editing in sequences and alignments. Finally, binary matrices of editing positions can be produced that may be used for downstream (e.g. phylogenetic) analyses.

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