2016
DOI: 10.1128/mmbr.00005-16
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The Epigenetic Pathways to Ribosomal DNA Silencing

Abstract: SUMMARYHeterochromatin is the transcriptionally repressed portion of eukaryotic chromatin that maintains a condensed appearance throughout the cell cycle. At sites of ribosomal DNA (rDNA) heterochromatin, epigenetic states contribute to gene silencing and genome stability, which are required for proper chromosome segregation and a normal life span. Here, we focus on recent advances in the epigenetic regulation of rDNA silencing inSaccharomyces cerevisiaeand in mammals, including regulation by several histone m… Show more

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Cited by 69 publications
(60 citation statements)
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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%
See 1 more Smart Citation
“…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%
“…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%
“…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%
“…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%