The Epigenetic Pathways to Ribosomal DNA Silencing

Srivastava, Rakesh K.; Srivastava, R. C.; Ahn, Shihyun

doi:10.1128/mmbr.00005-16

Cited by 69 publications

(60 citation statements)

References 222 publications

(306 reference statements)

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“…Finally, we tested whether the mcm2‐3A and pol1‐4A mutations affected silencing of a URA3 marker gene that had been inserted into one copy of the rDNA repeats on chromosome 12. Interestingly, gene silencing in the rDNA is mechanistically distinct from silencing at telomeres and the silent mating‐type loci (Srivastava et al , ). The URA3 gene was silenced when inserted into either the NTS1 or NTS2 sequences of an rDNA repeat, and silencing at NTS1 was relieved in cells that lack the type I topoisomerase Top1 (Fig EV3), as reported previously (Huang et al , ).…”

Section: Resultsmentioning

confidence: 99%

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Histone H2A‐H2B binding by Pol α in the eukaryotic replisome contributes to the maintenance of repressive chromatin

et al. 2018

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The eukaryotic replisome disassembles parental chromatin at DNA replication forks, but then plays a poorly understood role in the re‐deposition of the displaced histone complexes onto nascent DNA. Here, we show that yeast DNA polymerase α contains a histone‐binding motif that is conserved in human Pol α and is specific for histones H2A and H2B. Mutation of this motif in budding yeast cells does not affect DNA synthesis, but instead abrogates gene silencing at telomeres and mating‐type loci. Similar phenotypes are produced not only by mutations that displace Pol α from the replisome, but also by mutation of the previously identified histone‐binding motif in the CMG helicase subunit Mcm2, the human orthologue of which was shown to bind to histones H3 and H4. We show that chromatin‐derived histone complexes can be bound simultaneously by Mcm2, Pol α and the histone chaperone FACT that is also a replisome component. These findings indicate that replisome assembly unites multiple histone‐binding activities, which jointly process parental histones to help preserve silent chromatin during the process of chromosome duplication.

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Section: Resultsmentioning

confidence: 99%

“…Gene silencing in the rDNA is considerably more complex than at the telomeric and silent mating-type loci (Huang & Moazed, 2003;Huang et al, 2006;Srivastava et al, 2016). Although the Sir2 histone deacetylase still plays an important role, both Sir3 and Sir4 are dispensable for rDNA silencing.…”

Section: Discussionmentioning

confidence: 99%

Histone H2A‐H2B binding by Pol α in the eukaryotic replisome contributes to the maintenance of repressive chromatin

et al. 2018

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“…The polymorphic restriction mapping likely results from methylation of the Poly R site, as predicted CpG methylation sites are found immediately flanking this site, and some combinations of methylation block EcoRI activity. In support of this hypothesis, levels of 18S gene methylation have been found to be high in patients with ovarian cancer (Srivastava et al, 2016). Further complicating the nDNA mapping, the 18S rDNA sequence is highly repetitive and therefore single nucleotide polymorphisms (SNPs) at Poly R could also contribute to unexpected cleavage patterns.…”

Section: Of 22mentioning

confidence: 99%

“…SJCRH30 cells were grown according to ATCC recommendations and DPBS-washed pellets were processed using the whole-cell DNA extraction method. The 18S ribosomal DNA (rDNA) sequence is highly repetitive in the human nuclear genome, with 600 to 800 copies per diploid human genome (Srivastava, Srivastava, & Ahn, 2016). One of the three EcoRI sites in the 18S region is polymorphic (Poly R; labeled as R** in Fig.…”

Section: Of 22mentioning

confidence: 99%

Analysis of Human Mitochondrial DNA Content by Southern Blotting and Nonradioactive Probe Hybridization

Wheeler

Young

2019

CP Toxicology

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A single cell can contain several thousand copies of the mitochondrial DNA genome or mtDNA. Tools for assessing mtDNA content are necessary for clinical and toxicological research, as mtDNA depletion is linked to genetic disease and drug toxicity. For instance, mtDNA depletion syndromes are typically fatal childhood disorders that are characterized by severe declines in mtDNA content in affected tissues. Mitochondrial toxicity and mtDNA depletion have also been reported in human immunodeficiency virus–infected patients treated with certain nucleoside reverse transcriptase inhibitors. Further, cell culture studies have demonstrated that exposure to oxidative stress stimulates mtDNA degradation. Here we outline a Southern blot and nonradioactive digoxigenin‐labeled probe hybridization method to estimate mtDNA content in human genomic DNA samples. © 2019 by John Wiley & Sons, Inc.

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“…Each repeat encodes 35S rRNA synthesized by RNA Pol I and the Pol III-transcribed 5S rRNA. In exponentially growing cells, more than half of the rDNA is transcriptionally silenced (144)(145)(146)(147). The remaining fraction constitutes active rRNA genes that are largely depleted of nucleosomes but instead loaded with RNA Pol I and HMO1, with HMO1 stabilizing the open chromatin state in the absence of RNA Pol I transcription (145,148).…”

Section: Hmo1 Is a Component Of The Pol I Transcription Machinerymentioning

confidence: 99%

Yeast HMO1: Linker Histone Reinvented

Panday

Grove

2017

Microbiol Mol Biol Rev

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SUMMARY Eukaryotic genomes are packaged in chromatin. The higher-order organization of nucleosome core particles is controlled by the association of the intervening linker DNA with either the linker histone H1 or high mobility group box (HMGB) proteins. While H1 is thought to stabilize the nucleosome by preventing DNA unwrapping, the DNA bending imposed by HMGB may propagate to the nucleosome to destabilize chromatin. For metazoan H1, chromatin compaction requires its lysine-rich C-terminal domain, a domain that is buried between globular domains in the previously characterized yeast Saccharomyces cerevisiae linker histone Hho1p. Here, we discuss the functions of S. cerevisiae HMO1, an HMGB family protein unique in containing a terminal lysine-rich domain and in stabilizing genomic DNA. On ribosomal DNA (rDNA) and genes encoding ribosomal proteins, HMO1 appears to exert its role primarily by stabilizing nucleosome-free regions or “fragile” nucleosomes. During replication, HMO1 likewise appears to ensure low nucleosome density at DNA junctions associated with the DNA damage response or the need for topoisomerases to resolve catenanes. Notably, HMO1 shares with the mammalian linker histone H1 the ability to stabilize chromatin, as evidenced by the absence of HMO1 creating a more dynamic chromatin environment that is more sensitive to nuclease digestion and in which chromatin-remodeling events associated with DNA double-strand break repair occur faster; such chromatin stabilization requires the lysine-rich extension of HMO1. Thus, HMO1 appears to have evolved a unique linker histone-like function involving the ability to stabilize both conventional nucleosome arrays as well as DNA regions characterized by low nucleosome density or the presence of noncanonical nucleosomes.

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The Epigenetic Pathways to Ribosomal DNA Silencing

Cited by 69 publications

References 222 publications

Histone H2A‐H2B binding by Pol α in the eukaryotic replisome contributes to the maintenance of repressive chromatin

Histone H2A‐H2B binding by Pol α in the eukaryotic replisome contributes to the maintenance of repressive chromatin

Analysis of Human Mitochondrial DNA Content by Southern Blotting and Nonradioactive Probe Hybridization

Yeast HMO1: Linker Histone Reinvented

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