R Loops Are Linked to Histone H3 S10 Phosphorylation and Chromatin Condensation

Castellano‐Pozo, Maikel; Santos-Pereira, José M.; Rondón, Ana G.; Barroso, Sónia; Andújar, Eloísa; Pérez-Alegre, Mónica; García‐Muse, Tatiana; Aguilera, Andrés

doi:10.1016/j.molcel.2013.10.006

Cited by 241 publications

(230 citation statements)

References 43 publications

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“…DNA:RNA hybrid formation was shown to induce H3S10 phosphorylation (H3S10P) (Castellano-Pozo et al 2013), a chromatin mark that reduces HP1 binding to H3K9 methylated nucleosomes and interferes with heterochromatin formation and silencing (Fischle et al 2005;Kloc et al 2008). We determined H3S10P levels; however, we observed reduction of H3S10P in caf1Δdcr1Δ cells at tlh (Supplemental Fig.…”

Section: Absence Of Rna Degradation Leads To Changes In Chromatin Orgmentioning

confidence: 93%

Accumulation of RNA on chromatin disrupts heterochromatic silencing

Brönner¹,

Salvi²,

Zocco³

et al. 2017

Genome Res.

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Long noncoding RNAs (lncRNAs) play a conserved role in regulating gene expression, chromatin dynamics, and cell differentiation. They serve as a platform for RNA interference (RNAi)-mediated heterochromatin formation or DNA methylation in many eukaryotic organisms. We found in Schizosaccharomyces pombe that heterochromatin is lost at transcribed regions in the absence of RNA degradation. We show that heterochromatic RNAs are retained on chromatin, form DNA: RNA hybrids, and need to be degraded by the Ccr4-Not complex or RNAi to maintain heterochromatic silencing. The Ccr4-Not complex is localized to chromatin independently of H3K9me and degrades chromatin-associated transcripts, which is required for transcriptional silencing. Overexpression of heterochromatic RNA, but not euchromatic RNA, leads to chromatin localization and loss of silencing of a distant ade6 reporter in wild-type cells. Our results demonstrate that chromatin-bound RNAs disrupt heterochromatin organization and need to be degraded in a process of heterochromatin formation.

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Section: Absence Of Rna Degradation Leads To Changes In Chromatin Orgmentioning

confidence: 93%

Accumulation of RNA on chromatin disrupts heterochromatic silencing

Brönner¹,

Salvi²,

Zocco³

et al. 2017

Genome Res.

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show abstract

“…Wang et al, 2012). Active Aurora B then phosphorylates Ser-10 of histone H3 (H3S10ph), which affects chromosome condensation and segregation (Yamagishi et al, 2010;Castellano-Pozo et al, 2013). A recent study reported that a mutation in the Arabidopsis thaliana Aurora1 gene results in a defect in meiotic chromosome segregation (Demidov et al, 2014), but the cellular defects of the aberrant meiosis were not described in detail.…”

Section: Introductionmentioning

confidence: 99%

Arabidopsis Cell Division Cycle 20.1 Is Required for Normal Meiotic Spindle Assembly and Chromosome Segregation

et al. 2015

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Cell division requires proper spindle assembly; a surveillance pathway, the spindle assembly checkpoint (SAC), monitors whether the spindle is normal and correctly attached to kinetochores. The SAC proteins regulate mitotic chromosome segregation by affecting CDC20 (Cell Division Cycle 20) function. However, it is unclear whether CDC20 regulates meiotic spindle assembly and proper homolog segregation. Here, we show that the Arabidopsis thaliana CDC20.1 gene is indispensable for meiosis and male fertility. We demonstrate that cdc20.1 meiotic chromosomes align asynchronously and segregate unequally and the metaphase I spindle has aberrant morphology. Comparison of the distribution of meiotic stages at different time points between the wild type and cdc20

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“…R loops form when an RNA molecule anneals to a homologous DNA sequence in the genome, generating a region of DNA:RNA hybrid and a displaced ssDNA. R loops can act as precursors to genomic instability, modulators of gene expression, and regulators of chromatin epigenetic marks (Huertas and Aguilera 2003;Li and Manley 2005;Nakama et al 2012;Castellano-Pozo et al 2013;Sun et al 2013;Wahba et al 2013). Given the centrality of R loops in many genomic functions, the precise mapping of where they form and understanding why they form are important biological questions.…”

mentioning

confidence: 99%

S1-DRIP-seq identifies high expression and polyA tracts as major contributors to R-loop formation

et al. 2016

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R loops form when transcripts hybridize to homologous DNA on chromosomes, yielding a DNA:RNA hybrid and a displaced DNA single strand. R loops impact the genome of many organisms, regulating chromosome stability, gene expression, and DNA repair. Understanding the parameters dictating R-loop formation in vivo has been hampered by the limited quantitative and spatial resolution of current genomic strategies for mapping R loops. We report a novel whole-genome method, S1-DRIP-seq (S1 nuclease DNA:RNA immunoprecipitation with deep sequencing), for mapping hybrid-prone regions in budding yeast Saccharomyces cerevisiae. Using this methodology, we identified ∼800 hybrid-prone regions covering 8% of the genome. Given the pervasive transcription of the yeast genome, this result suggests that R-loop formation is dictated by characteristics of the DNA, RNA, and/or chromatin. We successfully identified two features highly predictive of hybrid formation: high transcription and long homopolymeric dA:dT tracts. These accounted for >60% of the hybrid regions found in the genome. We demonstrated that these two factors play a causal role in hybrid formation by genetic manipulation. Thus, the hybrid map generated by S1-DRIP-seq led to the identification of the first global genomic features causal for R-loop formation in yeast.

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R Loops Are Linked to Histone H3 S10 Phosphorylation and Chromatin Condensation

Cited by 241 publications

References 43 publications

Accumulation of RNA on chromatin disrupts heterochromatic silencing

Accumulation of RNA on chromatin disrupts heterochromatic silencing

Arabidopsis Cell Division Cycle 20.1 Is Required for Normal Meiotic Spindle Assembly and Chromosome Segregation

S1-DRIP-seq identifies high expression and polyA tracts as major contributors to R-loop formation

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