Nucleosomes are well positioned in exons and carry characteristic histone modifications

Andersson, Robin; Enroth, Stefan; Rada-Iglesias, Álvaro; Wadelius, Claes; Komorowski, Jan

doi:10.1101/gr.092353.109

Cited by 289 publications

(331 citation statements)

References 52 publications

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“…Indeed, we observe enrichment for phosphorylated RNAPII at these sites (Supplemental Fig. S11), and the preferential positioning of nucleosomes at exon borders, reminiscent of 59 and 39 gene termini, has been recently reported (Andersson et al 2009;Nahkuri et al 2009;Schwartz et al 2009;Spies et al 2009;Tilgner et al 2009). …”

Section: Discussionmentioning

confidence: 92%

Regulated post-transcriptional RNA cleavage diversifies the eukaryotic transcriptome

Mercer¹,

Dinger²,

Bracken³

et al. 2010

Genome Res.

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The complexity of the eukaryotic transcriptome is generated by the interplay of transcription initiation, termination, alternative splicing, and other forms of post-transcriptional modification. It was recently shown that RNA transcripts may also undergo cleavage and secondary 59 capping. Here, we show that post-transcriptional cleavage of RNA contributes to the diversification of the transcriptome by generating a range of small RNAs and long coding and noncoding RNAs. Using genomewide histone modification and RNA polymerase II occupancy data, we confirm that the vast majority of intraexonic CAGE tags are derived from post-transcriptional processing. By comparing exonic CAGE tags to tissue-matched PARE data, we show that the cleavage and subsequent secondary capping is regulated in a developmental-stage-and tissue-specific manner. Furthermore, we find evidence of prevalent RNA cleavage in numerous transcriptomic data sets, including SAGE, cDNA, small RNA libraries, and deep-sequenced size-fractionated pools of RNA. These cleavage products include mRNA variants that retain the potential to be translated into shortened functional protein isoforms. We conclude that post-transcriptional RNA cleavage is a key mechanism that expands the functional repertoire and scope for regulatory control of the eukaryotic transcriptome.

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Section: Discussionmentioning

confidence: 92%

Regulated post-transcriptional RNA cleavage diversifies the eukaryotic transcriptome

Mercer¹,

Dinger²,

Bracken³

et al. 2010

Genome Res.

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“…Remarkably, the pattern of these alterations was not irregular, raising a question of the underlying mechanism. Apart from alterations of cross-exon protein interactions and/or RNA secondary/tertiary structure, chromatin and histone modifications have been recently shown to influence splicing [Andersson et al, 2009;Gama-Carvalho et al, 1997;Kolasinska-Zwierz et al, 2009;Kornblihtt et al, 2009;Schor et al, 2009;Tilgner et al, 2009]. Exon marking and nucleosome occupancy between exons and introns also show only ~1.5-fold differences and nucleosome occupancy improved exon recognition only to a limited degree [Spies et al, 2009].…”

Section: Discussionmentioning

confidence: 99%

Prediction of single‐nucleotide substitutions that result in exon skipping: identification of a splicing silencer inBRCA1exon 6

et al. 2011

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Missense, nonsense and translationally silent mtuations can inactivate genes by altering the inclusion of mutant exons in messenger RNA, but their overall fraction among disease-causing exonic substitutions is unknown. Here, we have systematically tested missense and silent mutations deposited in the BRCA1 mutation databases of unclassified variants for their effects on exon inclusion in the mRNA experimentally. The introduction of 21 BRCA1 variants in two minigene systems revealed a single example of

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“…Overall, the preference of methylation for exons in the various plant and animal species suggests that, like gene body methylation, exon methylation may be an ancestral condition. It has been recently shown that exons are enriched in nucleosome content relative to introns (23)(24)(25), so it is tempting to speculate that nucleosomes might act to guide DNA methyltransferases resulting in higher methylation levels on exons.…”

Section: Danio Rerio Mus Musculusmentioning

confidence: 99%

Conservation and divergence of methylation patterning in plants and animals

Feng

Cokus

Zhang³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

1,107

120

1,082

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Cytosine DNA methylation is a heritable epigenetic mark present in many eukaryotic organisms. Although DNA methylation likely has a conserved role in gene silencing, the levels and patterns of DNA methylation appear to vary drastically among different organisms. Here we used shotgun genomic bisulfite sequencing (BS-Seq) to compare DNA methylation in eight diverse plant and animal genomes. We found that patterns of methylation are very similar in flowering plants with methylated cytosines detected in all sequence contexts, whereas CG methylation predominates in animals. Vertebrates have methylation throughout the genome except for CpG islands. Gene body methylation is conserved with clear preference for exons in most organisms. Furthermore, genes appear to be the major target of methylation in Ciona and honey bee. Among the eight organisms, the green alga Chlamydomonas has the most unusual pattern of methylation, having non-CG methylation enriched in exons of genes rather than in repeats and transposons. In addition, the Dnmt1 cofactor Uhrf1 has a conserved function in maintaining CG methylation in both transposons and gene bodies in the mouse, Arabidopsis, and zebrafish genomes.BS-Seq | epigenetic profiling | DNA methylation | gene body methylation | UHRF1C ytosine DNA methylation is an epigenetic mark important in many gene regulatory systems, including genomic imprinting, X-chromosome inactivation, silencing of transposons and other repetitive DNA sequences, as well as expression of endogenous genes. Methylation is conserved in most major eukaryotic groups, including many plants, animals, and fungi, although it has been lost from certain model organisms such as the budding yeast Saccharomyces cerevisiae and nematode worm Caenorhabditis elegans (1-3). DNA methylation can be categorized into three types according to the sequence context of the cytosines, namely CG, CHG, and CHH (H = A, C, or T). CG methylation is maintained by conserved Dnmt1 DNA methyltransferase enzymes. CHH methylation, and, to some extent CHG methylation, is generally maintained by the activity of the conserved Dnmt3 methyltransferases, whereas high levels of CHG methylation seen in the model plant Arabidopsis are maintained by the plant-specific methyltransferase CMT3 (2, 3). Generally speaking, DNA methylation is thought to occur "globally" in vertebrates, with CG sites being heavily methylated genome-wide except for those in CpG islands, whereas invertebrates, plants, and fungi have "mosaic" methylation, characterized by interspersed methylated and unmethylated domains (4). These differences are an interesting starting point for studying divergence in methylation pathways and regulatory mechanisms; however, determining precise genomescale methylation patterns has been a challenge for complex genomes until the recent development of high-throughput sequencing technology. In this paper, we generated shotgun bisulfite sequencing data to profile DNA methylation in eight eukaryotic organisms. These organisms display wide variations in methylati...

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Nucleosomes are well positioned in exons and carry characteristic histone modifications

Cited by 289 publications

References 52 publications

Regulated post-transcriptional RNA cleavage diversifies the eukaryotic transcriptome

Regulated post-transcriptional RNA cleavage diversifies the eukaryotic transcriptome

Prediction of single‐nucleotide substitutions that result in exon skipping: identification of a splicing silencer inBRCA1exon 6

Conservation and divergence of methylation patterning in plants and animals

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