Chromatin organization marks exon-intron structure

Schwartz, Schraga; Meshorer, Eran; Ast, Gil

doi:10.1038/nsmb.1659

Cited by 568 publications

(624 citation statements)

References 57 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: 91%

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: 91%

Regulated post-transcriptional RNA cleavage diversifies the eukaryotic transcriptome

Mercer¹,

Dinger²,

Bracken³

et al. 2010

Genome Res.

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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.

1,113

119

1,049

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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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“…Although it is known that splicing occurs cotranscriptionally, it is far less well understood how changes in this chromatin template affect the reaction. Analysis of tiling array data has suggested that nucleosomes and, according to several of these studies, specific histone modifications are enriched in exon sequences, suggesting that there may be specific histone "marks" that are associated with splicing signals (1)(2)(3)(4)(5)(6)(7). Additionally, proteins that bind to methylated histones (H3K4me3 and H3K36me3) have been shown to facilitate the recruitment of snRNPs to the nascent transcript and influence efficiency of splicing and alternative splicing (8,9).…”

mentioning

confidence: 99%

Dynamic histone acetylation is critical for cotranscriptional spliceosome assembly and spliceosomal rearrangements

Gunderson

Merkhofer

Johnson

2011

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

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Assembly of the spliceosome onto pre-mRNA is a dynamic process involving the ordered exchange of snRNPs to form the catalytically active spliceosome. These ordered rearrangements have recently been shown to occur cotranscriptionally, while the RNA polymerase is still actively engaged with the chromatin template. We previously demonstrated that the histone acetyltransferase Gcn5 is required for U2 snRNP association with the branchpoint. Here we provide evidence that histone acetylation and deacetylation facilitate proper cotranscriptional association of spliceosomal snRNPs. As with GCN5, mutation or deletion of Gcn5-targeted histone H3 residues leads to synthetic lethality when combined with deletion of the genes encoding the U2 snRNP components Lea1 or Msl1. Gcn5 associates throughout intron-containing genes and, in the absence of the histone deacetylases Hos3 and Hos2, enhanced histone H3 acetylation is observed throughout the body of genes. Deletion of histone deacetylaces also results in persistent association of the U2 snRNP and a severe defect in the association of downstream factors. These studies show that cotranscriptional spliceosome rearrangements are driven by dynamic changes in the acetylation state of histones and provide a model whereby yeast spliceosome assembly is tightly coupled to histone modification.pre-mRNA splicing | Saccharomyces cerevisiae R emoval of noncoding sequences from premessenger RNA is achieved by the activity of a dynamic ribonucleoprotein complex, the spliceosome. As the spliceosomal snRNPs sequentially recognize sequences in the pre-mRNA, the spliceosome undergoes ATP-dependent rearrangement of its RNA and protein components. Recently, it has been recognized that splicing can occur cotranscriptionally, while the RNA polymerase is still actively engaged with the chromatin template.The monomeric units of chromatin, nucleosomes, are comprised of DNA wrapped around the core histones H3, H4, H2A, and H2B. Histones undergo extensive posttranslational modification on their N-terminal tails that affect compaction of DNA and binding of regulatory factors. Although it is known that splicing occurs cotranscriptionally, it is far less well understood how changes in this chromatin template affect the reaction. Analysis of tiling array data has suggested that nucleosomes and, according to several of these studies, specific histone modifications are enriched in exon sequences, suggesting that there may be specific histone "marks" that are associated with splicing signals (1-7). Additionally, proteins that bind to methylated histones (H3K4me3 and H3K36me3) have been shown to facilitate the recruitment of snRNPs to the nascent transcript and influence efficiency of splicing and alternative splicing (8, 9). The chromatin-bound mammalian SWI/SNF complex associates with components of the spliceosome and affects alternative splicing (10, 11). Although these studies suggest a role for histone modifications in mammalian alternative splicing, there has been little analysis of their roles in constitu...

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Chromatin organization marks exon-intron structure

Cited by 568 publications

References 57 publications

Regulated post-transcriptional RNA cleavage diversifies the eukaryotic transcriptome

Regulated post-transcriptional RNA cleavage diversifies the eukaryotic transcriptome

Conservation and divergence of methylation patterning in plants and animals

Dynamic histone acetylation is critical for cotranscriptional spliceosome assembly and spliceosomal rearrangements

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