Nucleosome Distribution near the 3′ Ends of Genes in the Human Genome

Huang, Huan; Liu, Hongde; Sun, Xiao

doi:10.1271/bbb.130399

Cited by 10 publications

(13 citation statements)

References 36 publications

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“…2h), suggesting that the nucleosomal arrangement was important to a directional process on the DNA molecule (presumably transcription). This nucleosomal arrangement is very similar to that seen in human and yeast genomes, where nucleosomes are also depleted on polyadenylation sites [61, 62]. A similar organization was also seen in L. major , although the observed NDR was present immediately upstream of the PAS [57].…”

Section: Resultssupporting

confidence: 70%

Well-positioned nucleosomes punctuate polycistronic pol II transcription units and flank silent VSG gene arrays in Trypanosoma brucei

Maree

Povelones

Clark

et al. 2017

Epigenetics & Chromatin

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BackgroundThe compaction of DNA in chromatin in eukaryotes allowed the expansion of genome size and coincided with significant evolutionary diversification. However, chromatin generally represses DNA function, and mechanisms coevolved to regulate chromatin structure and its impact on DNA. This included the selection of specific nucleosome positions to modulate accessibility to the DNA molecule. Trypanosoma brucei, a member of the Excavates supergroup, falls in an ancient evolutionary branch of eukaryotes and provides valuable insight into the organization of chromatin in early genomes.ResultsWe have mapped nucleosome positions in T. brucei and identified important differences compared to other eukaryotes: The RNA polymerase II initiation regions in T. brucei do not exhibit pronounced nucleosome depletion, and show little evidence for defined −1 and +1 nucleosomes. In contrast, a well-positioned nucleosome is present directly on the splice acceptor sites within the polycistronic transcription units. The RNA polyadenylation sites were depleted of nucleosomes, with a single well-positioned nucleosome present immediately downstream of the predicted sites. The regions flanking the silent variant surface glycoprotein (VSG) gene cassettes showed extensive arrays of well-positioned nucleosomes, which may repress cryptic transcription initiation. The silent VSG genes themselves exhibited a less regular nucleosomal pattern in both bloodstream and procyclic form trypanosomes. The DNA replication origins, when present within silent VSG gene cassettes, displayed a defined nucleosomal organization compared with replication origins in other chromosomal core regions.ConclusionsOur results indicate that some organizational features of chromatin are evolutionarily ancient, and may already have been present in the last eukaryotic common ancestor.Electronic supplementary materialThe online version of this article (doi:10.1186/s13072-017-0121-9) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 70%

Well-positioned nucleosomes punctuate polycistronic pol II transcription units and flank silent VSG gene arrays in Trypanosoma brucei

Maree

Povelones

Clark

et al. 2017

Epigenetics & Chromatin

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“…We acknowledge that CUT 3′ heterogeneity may affect the assessment of CUT 3′ NFRs by metagene analysis due to a lack of discrete and consistent TTS usage. We note that a similar difference between coding and non-coding gene 3′ nucleosome structure has also been observed in humans [ 35 ]. Interestingly, when we profile the 3′ nucleosome occupancy of yeast ncRNAs known as stable unannotated transcripts (SUTs) [ 11 ] (Additional file 4 : Figure S4,) we see only moderate 3′ nucleosome depletion.…”

Section: Resultssupporting

confidence: 71%

Survey of cryptic unstable transcripts in yeast

Vera

Dowell

2016

BMC Genomics

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BackgroundCryptic unstable transcripts (CUTs) are a largely unexplored class of nuclear exosome degraded, non-coding RNAs in budding yeast. It is highly debated whether CUT transcription has a functional role in the cell or whether CUTs represent noise in the yeast transcriptome.We sought to ascertain the extent of conserved CUT expression across a variety of Saccharomyces yeast strains to further understand and characterize the nature of CUT expression.ResultsWe sequenced the WT and rrp6Δ transcriptomes of three S.cerevisiae strains: S288c, Σ1278b, JAY291 and the S.paradoxus strain N17 and utilized a hidden Markov model to annotate CUTs in these four strains. Utilizing a four-way genomic alignment we identified a large population of CUTs with conserved syntenic expression across all four strains. By identifying configurations of gene-CUT pairs, where CUT expression originates from the gene 5’ or 3′ nucleosome free region, we observed distinct gene expression trends specific to these configurations which were most prevalent in the presence of conserved CUT expression. Divergent pairs correlate with higher expression of genes, and convergent pairs correlate with reduced gene expression.ConclusionsOur RNA-seq based method has greatly expanded upon previous CUT annotations in S.cerevisiae underscoring the extensive and pervasive nature of unstable transcription. Furthermore we provide the first assessment of conserved CUT expression in yeast and globally demonstrate possible modes of CUT-based regulation of gene expression.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2622-5) contains supplementary material, which is available to authorized users.

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“…However, the molecular mechanism of how 3 0 UTR lengths are modulated by mTOR activity remains elusive. While more evidence is needed for mammalian systems, APA is likely to be affected by a variety of external and internal cues, including the local chromatin structure, nucleosome positioning, DNA methylation, and histone modifications (78). Therefore, epigenetic marks in cancer cells should also be taken into consideration to better understand the extent and mechanisms of deregulated APA in cancer.…”

Section: Possible Inducers Of Apamentioning

confidence: 99%

Alternative Polyadenylation: Another Foe in Cancer

Erson-Bensan

Can

2016

Molecular Cancer Research

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Advancements in sequencing and transcriptome analysis methods have led to seminal discoveries that have begun to unravel the complexity of cancer. These studies are paving the way toward the development of improved diagnostics, prognostic predictions, and targeted treatment options. However, it is clear that pieces of the cancer puzzle are still missing. In an effort to have a more comprehensive understanding of the development and progression of cancer, we have come to appreciate the value of the noncoding regions of our genomes, partly due to the discovery of miRNAs and their significance in gene regulation. Interestingly, the miRNA-mRNA interactions are not solely dependent on variations in miRNA levels. Instead, the majority of genes harbor multiple polyadenylation signals on their 3 0 UTRs (untranslated regions) that can be differentially selected on the basis of the physiologic state of cells, resulting in alternative 3 0 UTR isoforms. Deregulation of alternative polyadenylation (APA) has increasing interest in cancer research, because APA generates mRNA 3 0 UTR isoforms with potentially different stabilities, subcellular localizations, translation efficiencies, and functions. This review focuses on the link between APA and cancer and discusses the mechanisms as well as the tools available for investigating APA events in cancer. Overall, detection of deregulated APA-generated isoforms in cancer may implicate some proto-oncogene activation cases of unknown causes and may help the discovery of novel cases; thus, contributing to a better understanding of molecular mechanisms of cancer. Mol Cancer Res; 14(6); 507-17. Ó2016 AACR.

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Nucleosome Distribution near the 3′ Ends of Genes in the Human Genome

Cited by 10 publications

References 36 publications

Well-positioned nucleosomes punctuate polycistronic pol II transcription units and flank silent VSG gene arrays in Trypanosoma brucei

Well-positioned nucleosomes punctuate polycistronic pol II transcription units and flank silent VSG gene arrays in Trypanosoma brucei

Survey of cryptic unstable transcripts in yeast

Alternative Polyadenylation: Another Foe in Cancer

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