Nucleosomes are preferentially positioned at exons in somatic and sperm cells

Nahkuri, Satu; Taft, Ryan J.; Mattick, John S.

doi:10.4161/cc.8.20.9916

Cited by 96 publications

(93 citation statements)

References 29 publications

(42 reference statements)

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“…We first analyzed the distribution of nucleosome density over all internal exons. In agreement with previous reports (Andersson et al 2009;Nahkuri et al 2009;Schwartz et al 2009;Spies et al 2009;Tilgner et al 2009), an obvious peak of nucleosome density centered on the exon and surrounded by regions of lower density in the flanking introns was observed ( Fig. 2A).…”

Section: Resultssupporting

confidence: 81%

“…Nevertheless, nucleosome positioning is highly dynamic and its regulation is crucial to control chromatin accessibility and recruitment of chromatin modifiers and transcription factors (Ballaré et al 2013b;Becker and Workman 2013;Bartholomew 2014). Genomewide studies correlated chromatin structure with the exonintron organization of the genes and argued that nucleosomes are preferentially positioned in exons compared with introns in a variety of species, from worms to humans (Andersson et al 2009;Nahkuri et al 2009;Schwartz et al 2009;Spies et al 2009;Tilgner et al 2009). While the pattern of nucleosome occupancy at the transcription initiation and termination sites (TSS and TTS, respectively) is tightly connected with gene expression levels, nucleosome positioning over internal exons seems independent of transcription changes and levels of expression of the gene (Tilgner et al 2009).…”

Section: Introductionmentioning

confidence: 99%

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Relationship between nucleosome positioning and progesterone-induced alternative splicing in breast cancer cells

Iannone

Pohl

Papasaikas

et al. 2015

RNA

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Splicing of mRNA precursors can occur cotranscriptionally and it has been proposed that chromatin structure influences splice site recognition and regulation. Here we have systematically explored potential links between nucleosome positioning and alternative splicing regulation upon progesterone stimulation of breast cancer cells. We confirm preferential nucleosome positioning in exons and report four distinct profiles of nucleosome density around alternatively spliced exons, with RNA polymerase II accumulation closely following nucleosome positioning. Hormone stimulation induces switches between profile classes, correlating with a subset of alternative splicing changes. Hormone-induced exon inclusion often correlates with higher nucleosome occupancy at the exon or the preceding intronic region and with higher RNA polymerase II accumulation. In contrast, exons skipped upon hormone stimulation display low nucleosome densities even before hormone treatment, suggesting that chromatin structure primes alternative splicing regulation. Skipped exons frequently harbor binding sites for hnRNP AB, a hormone-induced splicing regulator whose knock down prevents some hormone-induced skipping events. Collectively, our results argue that a variety of chromatin architecture mechanisms can influence alternative splicing decisions.

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Section: Resultssupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Relationship between nucleosome positioning and progesterone-induced alternative splicing in breast cancer cells

Iannone

Pohl

Papasaikas

et al. 2015

RNA

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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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“…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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Nucleosomes are preferentially positioned at exons in somatic and sperm cells

Cited by 96 publications

References 29 publications

Relationship between nucleosome positioning and progesterone-induced alternative splicing in breast cancer cells

Relationship between nucleosome positioning and progesterone-induced alternative splicing in breast cancer cells

Regulated post-transcriptional RNA cleavage diversifies the eukaryotic transcriptome

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

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