Cohesion promotes nucleolar structure and function

Harris, Bethany; Bose, Tania; Lee, Kenneth K.; Wang, Fei; Lü, Shuai; Ross, Rhonda Trimble; Zhang, Ying; French, Sarah L.; Beyer, Ann L.; Slaughter, Brian D.; Unruh, Jay R.; Gerton, Jennifer L.

doi:10.1091/mbc.e13-07-0377

Cited by 48 publications

(49 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This phenotype resembles the nucleolar alterations seen in Roberts syndrome, a known cohesinopathy. There, mutation in the human ESCO2 gene inactivates the SMC3 acetyltransferase required to induce cohesiveness of the cohesin ring complex (Harris et al, 2014). Roberts syndrome nuclei display strikingly similar gross nucleolar architecture, with disrupted ribosomal RNA expression and ribosome biogenesis.…”

Section: Combined Smc3 Haploinsufficiency and Flt3-itd Results In Potmentioning

confidence: 99%

Dose-dependent role of the cohesin complex in normal and malignant hematopoiesis

Viny¹,

Ott²,

Spitzer³

et al. 2015

J Cell Biol

View full text Add to dashboard Cite

Cohesin complex members have recently been identified as putative tumor suppressors in hematologic and epithelial malignancies. The cohesin complex guides chromosome segregation; however, cohesin mutant leukemias do not show genomic instability. We hypothesized that reduced cohesin function alters chromatin structure and disrupts cis-regulatory architecture of hematopoietic progenitors. We investigated the consequences of Smc3 deletion in normal and malignant hematopoiesis. Biallelic Smc3 loss induced bone marrow aplasia with premature sister chromatid separation and revealed an absolute requirement for cohesin in hematopoietic stem cell (HSC) function. In contrast, Smc3 haploinsufficiency increased self-renewal in vitro and in vivo, including competitive transplantation. Smc3 haploinsufficiency reduced coordinated transcriptional output, including reduced expression of transcription factors and other genes associated with lineage commitment. Smc3 haploinsufficiency cooperated with Flt3-ITD to induce acute leukemia in vivo, with potentiated Stat5 signaling and altered nucleolar topology. These data establish a dose dependency for cohesin in regulating chromatin structure and HSC function.

show abstract

Section: Combined Smc3 Haploinsufficiency and Flt3-itd Results In Potmentioning

confidence: 99%

Dose-dependent role of the cohesin complex in normal and malignant hematopoiesis

Viny¹,

Ott²,

Spitzer³

et al. 2015

J Cell Biol

View full text Add to dashboard Cite

show abstract

“…The repeats that are involved in this multiplex interaction need not be adjacent, and the overall structure of the interaction resembles the replication-factory model proposed by Cook (46). Nucleolar organization and tDNA clustering are both facilitated by proteins, including cohesin, that are involved in mediating chromosome structure (47,48). Interestingly, we found that replacement of the tK gene on the boundary of the RPA135 intergenic region also contributed to increased variation in the RPA135-IGS1 interaction frequency.…”

Section: Discussionmentioning

confidence: 72%

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

View full text Add to dashboard Cite

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...

show abstract

“…The scale bar represents 0.2 μm. The data for WT and eco1-W216G strains were first published in Harris et al 2.B FOB1 deletion does not rescue cohesin acetylation in the eco1 mutant. The cohesin complex was immunoprecipitated with α-Myc affinity gel and then analyzed by western blotting with α-acetyl-lysine antibody for Smc3 acetylation level (upper panel).…”

Section: Resultsmentioning

confidence: 80%

“…The scale bar represents 0.2 μm. The data for WT and eco1-W216G strains were first published in Harris et al 2.…”

Section: Resultsmentioning

confidence: 99%

The cohesin acetyltransferase Eco1 coordinates rDNA replication and transcription

et al. 2014

Self Cite

View full text Add to dashboard Cite

Eco1 is the acetyltransferase that establishes sister-chromatid cohesion during DNA replication. A budding yeast strain with an eco1 mutation that genocopies Roberts syndrome has reduced ribosomal DNA (rDNA) transcription and a transcriptional signature of starvation. We show that deleting FOB1—a gene that encodes a replication fork-blocking protein specific for the rDNA region—rescues rRNA production and partially rescues transcription genome-wide. Further studies show that deletion of FOB1 corrects the genome-wide replication defects, nucleolar structure, and rDNA segregation that occur in the eco1 mutant. Our study highlights that the presence of cohesin at the rDNA locus has a central role in controlling global DNA replication and gene expression.

show abstract

Cohesion promotes nucleolar structure and function

Cited by 48 publications

References 40 publications

Dose-dependent role of the cohesin complex in normal and malignant hematopoiesis

Dose-dependent role of the cohesin complex in normal and malignant hematopoiesis

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

The cohesin acetyltransferase Eco1 coordinates rDNA replication and transcription

Contact Info

Product

Resources

About