Cohesinopathy mutations disrupt the subnuclear organization of chromatin

Gard, Scarlett; Light, William H.; Xiong, Bo; Bose, Tania; McNairn, Adrian J.; Harris, Bethany; Fleharty, Brian; Seidel, Chris; Brickner, Jason H.; Gerton, Jennifer L.

doi:10.1083/jcb.200906075

Cited by 81 publications

(74 citation statements)

References 39 publications

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“…Roles for Pol III promoter elements in simple eukaryote chromatin structure have been also observed in S. pombe (Noma et al 2006). In addition to structural roles for ETCs, tDNAs establish heterochromatic boundaries (Donze and Kamakaka 2001), phase nucleosomes (Morse et al 1992), bind condensins (D'Ambrosio et al 2008;Haeusler et al 2008;Gard et al 2009), repress transcription of neighboring Pol IItranscribed genes (Kinsey and Sandmeyer 1991;Hull et al 1994), undergo ectopic recombination (Munz et al 1982), and disrupt progression of downstream replication forks (Deshpande and Newlon 1996).…”

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confidence: 99%

Retrotransposon profiling of RNA polymerase III initiation sites

Qi¹,

Daily²,

Nguyen³

et al. 2012

Genome Res.

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Although retroviruses are relatively promiscuous in choice of integration sites, retrotransposons can display marked integration specificity. In yeast and slime mold, some retrotransposons are associated with tRNA genes (tDNAs). In the Saccharomyces cerevisiae genome, the long terminal repeat retrotransposon Ty3 is found at RNA polymerase III (Pol III) transcription start sites of tDNAs. Ty1, 2, and 4 elements also cluster in the upstream regions of these genes. To determine the extent to which other Pol III-transcribed genes serve as genomic targets for Ty3, a set of 10,000 Ty3 genomic retrotranspositions were mapped using high-throughput DNA sequencing. Integrations occurred at all known tDNAs, two tDNA relics (iYGR033c and ZOD1), and six non-tDNA, Pol III-transcribed types of genes (RDN5, SNR6, SNR52, RPR1, RNA170, and SCR1). Previous work in vitro demonstrated that the Pol III transcription factor (TF) IIIB is important for Ty3 targeting. However, seven loci that bind the TFIIIB loader, TFIIIC, were not targeted, underscoring the unexplained absence of TFIIIB at those sites. Ty3 integrations also occurred in two open reading frames not previously associated with Pol III transcription, suggesting the existence of a small number of additional sites in the yeast genome that interact with Pol III transcription complexes.

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confidence: 99%

Retrotransposon profiling of RNA polymerase III initiation sites

Qi¹,

Daily²,

Nguyen³

et al. 2012

Genome Res.

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“…The GAL2 locus is close to the rDNA locus and is positioned within or adjacent to the nucleolus. 37,38 This example further highlights how chromosome structure can create micro-domains or sub-compartments of the nucleus.…”

Section: Introductionmentioning

confidence: 99%

Interchromosomal clustering of active genes at the nuclear pore complex

Brickner

2012

Nucleus

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“…This raises the possibility that the RPA135-IGS1 interaction is facilitated in part by tDNA clustering at the nucleolar periphery. Therefore, the chromosome structuring mechanisms that contribute to tDNA clustering (28,49) and nucleolar organization may also work in conjunction with the factors that we identify here (Msn2 and elements III and VII) to promote the RPA135-IGS1 interaction.…”

Section: Discussionmentioning

confidence: 94%

A Sequence-Specific Interaction between the Saccharomyces cerevisiae rRNA Gene Repeats and a Locus Encoding an RNA Polymerase I Subunit Affects Ribosomal DNA Stability

Cahyani

Cridge

Engelke

et al. 2015

Molecular and Cellular Biology

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The spatial organization of eukaryotic genomes is linked to their functions. However, how individual features of the global spatial structure contribute to nuclear function remains largely unknown. We previously identified a high-frequency interchromosomal interaction within the Saccharomyces cerevisiae genome that occurs between the intergenic spacer of the ribosomal DNA (rDNA) repeats and the intergenic sequence between the locus encoding the second largest RNA polymerase I subunit and a lysine tRNA gene [i.e., RPA135-tK(CUU)P]. Here, we used quantitative chromosome conformation capture in combination with replacement mapping to identify a 75-bp sequence within the RPA135-tK(CUU)P intergenic region that is involved in the interaction. We demonstrate that the RPA135-IGS1 interaction is dependent on the rDNA copy number and the Msn2 protein. Surprisingly, we found that the interaction does not govern RPA135 transcription. Instead, replacement of a 605-bp region within the RPA135-tK(CUU)P intergenic region results in a reduction in the RPA135-IGS1 interaction level and fluctuations in rDNA copy number. We conclude that the chromosomal interaction that occurs between the RPA135-tK(CUU)P and rDNA IGS1 loci stabilizes rDNA repeat number and contributes to the maintenance of nucleolar stability. Our results provide evidence that the DNA loci involved in chromosomal interactions are composite elements, sections of which function in stabilizing the interaction or mediating a functional outcome. There are strong links between the spatial organization of a genome and its function (reviewed in references 1 to 3). This spatial organization is dynamic and specific for particular cell types and stages of the cell cycle (4-6). Genome spatial organization has been proposed to result from the physical properties of the chromosomes (e.g., volume and flexibility), the proteins (e.g., DNA binding and aggregation), and the nucleic acids (e.g., ability to form triplexes) that are present within the limited volume of the nucleus (7-10). While global genome structure contributes to cell identity (5) and differentiation and cycling (6), the contributions that individual contacts (i.e., interactions) between chromosomal loci make to genome function remain poorly understood. Here, we characterize a high-frequency interaction between the yeast rRNA genes (rDNA) and a locus encoding an RNA polymerase I subunit, RPA135 (Fig. 1A).In Saccharomyces cerevisiae, the rDNA is arranged as 150 to 200 tandem repeats on the long arm of chromosome XII (Chr XII) (11). Each of these tandemly arranged rDNA repeats consists of genes that encode the 35S and 5S rRNAs and two intergenic sequences, IGS1 and IGS2 (Fig. 1A). The rDNA is transcribed by two RNA polymerases: RNA polymerase I (RNAP I), which transcribes the 35S rRNA precursor, and RNAP III, which transcribes the 5S rRNA. Transcription of the rDNA by RNAP I is responsible for the majority of transcription in a cell (reviewed in reference 12).The high rate of transcription and the repetitive structure...

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Cohesinopathy mutations disrupt the subnuclear organization of chromatin

Abstract: Nuclear morphology, chromosomal condensation, and transcriptional-mediated localization of genes to the nuclear periphery are disturbed by mutations in cohesin pathway genes.

Cited by 81 publications

References 39 publications

Retrotransposon profiling of RNA polymerase III initiation sites

Retrotransposon profiling of RNA polymerase III initiation sites

Interchromosomal clustering of active genes at the nuclear pore complex

A Sequence-Specific Interaction between the Saccharomyces cerevisiae rRNA Gene Repeats and a Locus Encoding an RNA Polymerase I Subunit Affects Ribosomal DNA Stability

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