Subnuclear Relocalization and Silencing of a Chromosomal Region by an Ectopic Ribosomal DNA Repeat

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2013 Nov 6

PMID 24191010

Citations 12

Authors

Tadas Jakociunas

Marie Domange Jordo

Mazhoura Ait Mebarek

Camilla Marie Bunner

Janne Verhein-Hansen

Lene B Oddershede

Genevieve Thon

Affiliations

Soon will be listed here.

Abstract

Our research addresses the relationship between subnuclear localization and gene expression in fission yeast. We observed the relocalization of a heterochromatic region, the mating-type region, from its natural location at the spindle-pole body to the immediate vicinity of the nucleolus. Relocalization occurred in response to a DNA rearrangement replacing a boundary element (IR-R) with a ribosomal DNA repeat (rDNA-R). Gene expression was strongly silenced in the relocalized mating-type region through mechanisms that differ from those operating in wild type. Also different from the wild-type situation, programmed recombination events failed to take place in the rDNA-R mutant. Increased silencing and perinucleolar localization depended on Reb1, a DNA-binding protein with cognate sites in the rDNA. Reb1 was recently shown to mediate long-range interchromosomal interactions in the nucleus through dimerization, providing a mechanism for the observed relocalization. Replacing the full rDNA repeat with Reb1-binding sites, and using mutants lacking the histone H3K9 methyltransferase Clr4, indicated that the relocalized region was silenced redundantly by heterochromatin and another mechanism, plausibly antisense transcription, achieving a high degree of repression in the rDNA-R strain.

Citing Articles

New Functional Motifs for the Targeted Localization of Proteins to the Nucleolus in and Human Cells.

Ogienko A, Korepina M, Pindyurin A, Omelina E Int J Mol Sci. 2024; 25(2).

PMID: 38279227 PMC: 10817092. DOI: 10.3390/ijms25021230.

Distinct features of nucleolus-associated domains in mouse embryonic stem cells.

Bizhanova A, Yan A, Yu J, Zhu L, Kaufman P Chromosoma. 2020; 129(2):121-139.

PMID: 32219510 PMC: 7265113. DOI: 10.1007/s00412-020-00734-9.

Regulation of ectopic heterochromatin-mediated epigenetic diversification by the JmjC family protein Epe1.

Sorida M, Hirauchi T, Ishizaki H, Kaito W, Shimada A, Mori C PLoS Genet. 2019; 15(6):e1008129.

PMID: 31206516 PMC: 6576747. DOI: 10.1371/journal.pgen.1008129.

Nucleolus and chromatin.

Schofer C, Weipoltshammer K Histochem Cell Biol. 2018; 150(3):209-225.

PMID: 30046888 PMC: 6096769. DOI: 10.1007/s00418-018-1696-3.

Dependency of Heterochromatin Domains on Replication Factors.

Jahn L, Mason B, Brogger P, Toteva T, Nielsen D, Thon G G3 (Bethesda). 2017; 8(2):477-489.

PMID: 29187422 PMC: 5919735. DOI: 10.1534/g3.117.300341.

References

Ritland Politz J, Scalzo D, Groudine M . Something silent this way forms: the functional organization of the repressive nuclear compartment. Annu Rev Cell Dev Biol. 2013; 29:241-70. PMC: 3999972. DOI: 10.1146/annurev-cellbio-101512-122317. View

Torres-Rosell J, Sunjevaric I, Piccoli G, Sacher M, Eckert-Boulet N, Reid R . The Smc5-Smc6 complex and SUMO modification of Rad52 regulates recombinational repair at the ribosomal gene locus. Nat Cell Biol. 2007; 9(8):923-31. DOI: 10.1038/ncb1619. View

Fedoriw A, Starmer J, Yee D, Magnuson T . Nucleolar association and transcriptional inhibition through 5S rDNA in mammals. PLoS Genet. 2012; 8(1):e1002468. PMC: 3261910. DOI: 10.1371/journal.pgen.1002468. View

Krings G, Bastia D . swi1- and swi3-dependent and independent replication fork arrest at the ribosomal DNA of Schizosaccharomyces pombe. Proc Natl Acad Sci U S A. 2004; 101(39):14085-90. PMC: 521093. DOI: 10.1073/pnas.0406037101. View

Thon G, Bjerling K, NIELSEN I . Localization and properties of a silencing element near the mat3-M mating-type cassette of Schizosaccharomyces pombe. Genetics. 1999; 151(3):945-63. PMC: 1460531. DOI: 10.1093/genetics/151.3.945. View

Noma K , Allis C, Grewal S . Transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries. Science. 2001; 293(5532):1150-5. DOI: 10.1126/science.1064150. View

Nemeth A, Conesa A, Santoyo-Lopez J, Medina I, Montaner D, Peterfia B . Initial genomics of the human nucleolus. PLoS Genet. 2010; 6(3):e1000889. PMC: 2845662. DOI: 10.1371/journal.pgen.1000889. View

Sanchez J, Kim S, Huberman J . Ribosomal DNA replication in the fission yeast, Schizosaccharomyces pombe. Exp Cell Res. 1998; 238(1):220-30. DOI: 10.1006/excr.1997.3835. View

Cam H, Sugiyama T, Chen E, Chen X, FitzGerald P, Grewal S . Comprehensive analysis of heterochromatin- and RNAi-mediated epigenetic control of the fission yeast genome. Nat Genet. 2005; 37(8):809-19. DOI: 10.1038/ng1602. View

10.

Thon G, Klar A . Directionality of fission yeast mating-type interconversion is controlled by the location of the donor loci. Genetics. 1993; 134(4):1045-54. PMC: 1205573. DOI: 10.1093/genetics/134.4.1045. View

11.

Melekhovets Y, Shwed P, Nazar R . In vivo analyses of RNA polymerase I termination in Schizosaccharomyces pombe. Nucleic Acids Res. 1998; 25(24):5103-9. PMC: 147157. DOI: 10.1093/nar/25.24.5103. View

12.

Huang J, Brito I, Villen J, Gygi S, Amon A, Moazed D . Inhibition of homologous recombination by a cohesin-associated clamp complex recruited to the rDNA recombination enhancer. Genes Dev. 2006; 20(20):2887-901. PMC: 1619942. DOI: 10.1101/gad.1472706. View

13.

McStay B, Grummt I . The epigenetics of rRNA genes: from molecular to chromosome biology. Annu Rev Cell Dev Biol. 2008; 24:131-57. DOI: 10.1146/annurev.cellbio.24.110707.175259. View

14.

Simon P . Q-Gene: processing quantitative real-time RT-PCR data. Bioinformatics. 2003; 19(11):1439-40. DOI: 10.1093/bioinformatics/btg157. View

15.

Sullivan G, Bridger J, Cuthbert A, Newbold R, Bickmore W, McStay B . Human acrocentric chromosomes with transcriptionally silent nucleolar organizer regions associate with nucleoli. EMBO J. 2001; 20(11):2867-74. PMC: 125486. DOI: 10.1093/emboj/20.11.2867. View

16.

Stahl A, Hartung M, Fouet C . Chromosomal constitution of nucleolus-associated chromatin in man. Hum Genet. 1976; 35(1):27-34. DOI: 10.1007/BF00295616. View

17.

Buck S, Sandmeier J, Smith J . RNA polymerase I propagates unidirectional spreading of rDNA silent chromatin. Cell. 2003; 111(7):1003-14. DOI: 10.1016/s0092-8674(02)01193-5. View

18.

Arcangioli B . A site- and strand-specific DNA break confers asymmetric switching potential in fission yeast. EMBO J. 1998; 17(15):4503-10. PMC: 1170781. DOI: 10.1093/emboj/17.15.4503. View

19.

Cioci F, Vu L, Eliason K, Oakes M, Siddiqi I, Nomura M . Silencing in yeast rDNA chromatin: reciprocal relationship in gene expression between RNA polymerase I and II. Mol Cell. 2003; 12(1):135-45. DOI: 10.1016/s1097-2765(03)00262-4. View

20.

Tanizawa H, Iwasaki O, Tanaka A, Capizzi J, Wickramasinghe P, Lee M . Mapping of long-range associations throughout the fission yeast genome reveals global genome organization linked to transcriptional regulation. Nucleic Acids Res. 2010; 38(22):8164-77. PMC: 3001101. DOI: 10.1093/nar/gkq955. View