Centromere Biology: Transcription Goes on Stage

Perea-Resa, Carlos; Blower, Michael D.

doi:10.1128/mcb.00263-18

Cited by 57 publications

(54 citation statements)

References 79 publications

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“…We have shown that a specific locus that directs cohesin loading collaborates with the linear organisation of genes to fold a chromosomal domain into a structure competent for chromosome segregation. Non-coding transcription and enrichment of cohesin are common features of centromeric regions in many organisms, suggesting general principles may underlie their structure 28 . Potentially, the linear order of transcriptional units throughout a genome has evolved in such a way to broadly influence its function by locally controlling its architecture.…”

Section: Main Textmentioning

confidence: 99%

Convergent genes shape budding yeast pericentromeres

Paldi

Alver

Robertson

et al. 2019

Preprint

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AbstractThe 3D architecture of the genome governs its maintenance, expression and transmission. The conserved ring-shaped cohesin complex organises the genome by topologically linking distant loci on either a single DNA molecule or, after DNA replication, on separate sister chromatids to provide the cohesion that resists the pulling forces of spindle microtubules during mitosis1,2. Cohesin is highly enriched in specialized chromosomal domains surrounding centromeres, called pericentromeres3-7. However, the structural organisation of pericentromeres and implications for chromosome segregation are unknown. Here we report the 3D structure of budding yeast pericentromeres and establish the relationship between genome organisation and function. We find that convergent genes mark pericentromere borders and, together with core centromeres, define their structure and function by positioning cohesin. Centromeres load cohesin and convergent genes at pericentromere borders trap it. Each side of the pericentromere is organised into a looped conformation, with border convergent genes at the base. Microtubule attachment extends a single pericentromere loop, size-limited by convergent genes at its borders. Re-orienting genes at borders into a tandem configuration repositions cohesin, enlarges the pericentromere and impairs chromosome biorientation in mitosis. Thus, the linear arrangement of transcriptional units together with targeted cohesin loading at centromeres shapes pericentromeres into a structure competent for chromosome segregation during mitosis. Our results reveal the architecture of the chromosomal region within which kinetochores are embedded and the re-structuring caused by microtubule attachment. Furthermore, we establish a direct, causal relationship between 3D genome organization of a specific chromosomal domain and cellular function.

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Section: Main Textmentioning

confidence: 99%

Convergent genes shape budding yeast pericentromeres

Paldi

Alver

Robertson

et al. 2019

Preprint

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“…Understanding centromere function requires knowledge of the centromere-localized protein components as well as a clear understanding of the nature and dynamics of centromere chromatin. Although originally thought to be silent chromosome regions, centromeres are actively transcribed (Perea-Resa and Blower, 2018). Prior work has detected α-satellite transcription at centromere and pericentromere regions based on the localization of RNA polymerase II (Bergmann et al, 2012;Chan et al, 2012) and the production of centromere RNA transcripts (Chan et al, 2012;Saffery et al, 2003;Wong et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Alpha-satellite RNA transcripts are repressed by centromere-nucleolus associations

Bury

Moodie

McKay

et al. 2020

Preprint

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Centromeres play a fundamental role in chromosome segregation. Although originally thought to be silent chromosomal regions, centromeres are actively transcribed.However, the behavior and contributions of centromere-derived RNAs have remained unclear. Here, we used single-molecule fluorescence in-situ hybridization (smFISH) to detect alpha-satellite RNA transcripts in intact human cells. We find that alpha-satellite RNA smFISH foci fluctuate in their levels over the cell cycle and do not remain associated with centromeres, displaying localization consistent with other long noncoding RNAs. Our results demonstrate that alpha-satellite expression occurs through RNA Polymerase II-dependent transcription, but does not require centromere proteins and other cell division components. Instead, our work implicates centromere-nucleolar associations as the major factor regulating alpha-satellite expression. The fraction of nucleolar-localized centromeres inversely correlates with alpha-satellite transcripts levels, explaining variations in alpha-satellite RNA between cell lines. In addition, alphasatellite transcript levels increase substantially when the nucleolus is disrupted.Together, our results are inconsistent with a direct, physical role for alpha-satellite transcripts in cell division processes, and instead support a role for ongoing transcription in promoting centromere chromatin dynamics. The control of alpha-satellite transcription by centromere-nucleolar contacts provides a mechanism to modulate centromere transcription and chromatin dynamics across diverse cell states and conditions. Alexandrov, I., A. Kazakov, I. Tumeneva, V. Shepelev, and Y. Yurov. 2001. Alphasatellite DNA of primates: old and new families. Chromosoma. 110:253-266. . 2012. Epigenetic engineering: histone H3K9 acetylation is compatible with kinetochore structure and function. J Cell Sci. 125:411-421. . 2011. Epigenetic engineering shows H3K4me2 is required for HJURP targeting and CENP-A assembly on a synthetic human kinetochore. Embo J. 30:328-340. Biscotti, M.A., A. Canapa, M. Forconi, E. Olmo, and M. Barucca. 2015. Transcription of tandemly repetitive DNA: functional roles.

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“…Due to their localization near centromeres, satellite sequences are likely to be subject to strict regulation to maintain both genetic and epigenetic stability. While expression of pericentric satellites has been observed in many species, including yeast, plants and mammalian cells, it is clear that when satellites are expressed, their expression is highly regulated (reviewed in (Hall et al, 2012;Perea-Resa and Blower, 2018;Smurova and De Wulf, 2018)). The increased presence of satellite RNA has recently emerged as an indicator of instability, as demonstrated by satellite overexpression in cancer cells and tumor tissues (Hall et al, 2017;Ting et al, 2011;Zhu et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Ectopic expression of pericentric HSATII RNA results in nuclear RNA accumulation, MeCP2 recruitment, and cell division defects

Landers

Rabeler

Ferrari

et al. 2020

Preprint

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Within the pericentric regions of human chromosomes reside large arrays of tandemly repeated satellite sequences. Expression of the human pericentric satellite HSATII is prevented by extensive heterochromatin silencing in normal cells, yet in many cancer cells, HSATII RNA is aberrantly expressed and accumulates in large nuclear foci in cis. Expression and aggregation of HSATII RNA in cancer cells is concomitant with recruitment of key chromatin regulatory proteins including methyl-CpG binding protein 2 (MeCP2). While HSATII expression has been observed in a wide variety of cancer cell lines and tissues, the effect of its expression is unknown. We tested the effect of stable expression of HSATII RNA within cells that do not normally express HSATII. Ectopic HSATII expression in HeLa and primary fibroblast cells leads to focal accumulation of HSATII RNA in cis and triggers the accumulation of MeCP2 onto nuclear HSATII RNA bodies. Further, long-term expression of HSATII RNA leads to cell division defects including lagging chromosomes, chromatin bridges, and other chromatin defects.Thus, expression of HSATII RNA in normal cells phenocopies its nuclear accumulation in cancer cells and allows for the characterization of the cellular events triggered by aberrant expression of pericentric satellite RNA.

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Centromere Biology: Transcription Goes on Stage

Cited by 57 publications

References 79 publications

Convergent genes shape budding yeast pericentromeres

Convergent genes shape budding yeast pericentromeres

Alpha-satellite RNA transcripts are repressed by centromere-nucleolus associations

Ectopic expression of pericentric HSATII RNA results in nuclear RNA accumulation, MeCP2 recruitment, and cell division defects

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