The shelterin protein POT-1 anchors <i>Caenorhabditis elegans</i> telomeres through SUN-1 at the nuclear periphery

Ferreira, Helder; Towbin, Benjamin D.; Jegou, Thibaud; Gasser, Susan M.

doi:10.1083/jcb.201307181

Cited by 45 publications

(39 citation statements)

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“…Consistent with this interpretation, analysis of telomere positioning by FISH confirmed that the distal-most ends of chromosomes associate with the nuclear periphery (Ferreira et al 2013). These lamina-associated chromatin regions are the worm's version of LADs, and they are inherent to the DNA sequence rather than to the chromosomal location, because translocation of an arm region to the center of a chromosome retained the region's peripheral association (Ikegami et al 2010).…”

Section: Features Of C Elegans Chromosome Organizationmentioning

confidence: 56%

Cell Biology of theCaenorhabditis elegansNucleus

Cohen-Fix

Askjaer

2017

Genetics

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Studies on the Caenorhabditis elegans nucleus have provided fascinating insight to the organization and activities of eukaryotic cells. Being the organelle that holds the genetic blueprint of the cell, the nucleus is critical for basically every aspect of cell biology. The stereotypical development of C. elegans from a one cell-stage embryo to a fertile hermaphrodite with 959 somatic nuclei has allowed the identification of mutants with specific alterations in gene expression programs, nuclear morphology, or nuclear positioning. Moreover, the early C. elegans embryo is an excellent model to dissect the mitotic processes of nuclear disassembly and reformation with high spatiotemporal resolution. We review here several features of the C. elegans nucleus, including its composition, structure, and dynamics. We also discuss the spatial organization of chromatin and regulation of gene expression and how this depends on tight control of nucleocytoplasmic transport. Finally, the extensive connections of the nucleus with the cytoskeleton and their implications during development are described. Most processes of the C. elegans nucleus are evolutionarily conserved, highlighting the relevance of this powerful and versatile model organism to human biology.KEYWORDS Caenorhabditis elegans; chromatin; gene expression; lamin; LEM-domain proteins; LINC; P granule; nuclear pore complex; nuclear envelope; nucleocytoplasmic transport; nucleolus; WormBook TABLE OF CONTENTSAbstract 25 C. elegans as a model system to study cell biology of the nucleus 26 Structural components of the nucleus 27

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Section: Features Of C Elegans Chromosome Organizationmentioning

confidence: 56%

Cell Biology of theCaenorhabditis elegansNucleus

Cohen-Fix

Askjaer

2017

Genetics

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“…1E). The difference between males and hermaphrodites is particularly visible in the center of the chromosome, as telomeres appear to be anchored at the nuclear envelope similarly in both sexes (Ferreira et al 2013). Moreover, peripheral positioning does not appear to be rex sitespecific, as both rex and non-rex loci are peripherally located (Fig.…”

Section: Resultsmentioning

confidence: 99%

Differential spatial and structural organization of the X chromosome underlies dosage compensation in C. elegans

et al. 2014

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The adjustment of X-linked gene expression to the X chromosome copy number (dosage compensation [DC]) has been widely studied as a model of chromosome-wide gene regulation. In Caenorhabditis elegans, DC is achieved by twofold down-regulation of gene expression from both Xs in hermaphrodites. We show that in males, the single X chromosome interacts with nuclear pore proteins, while in hermaphrodites, the DC complex (DCC) impairs this interaction and alters X localization. Our results put forward a structural model of DC in which X-specific sequences locate the X chromosome in transcriptionally active domains in males, while the DCC prevents this in hermaphrodites.Supplemental material is available for this article.Received July 18, 2014; revised version accepted October 20, 2014. Throughout the animal kingdom, varied strategies have evolved to equalize expression of the X chromosome genes between sexes with different X to autosomes ratios, a process called dosage compensation (DC) (for review, see Ferrari et al. 2014). In Caenorhabditis elegans, genetic screens and RNA quantifications showed that DC occurs in hermaphrodites by twofold down-regulation of X-linked transcripts from both Xs (for review, see Strome et al. 2014). A number of mutants were isolated in which overexpression of X-linked genes led to hermaphroditespecific defects (dpy genes) or sex determination and DC deficiency (sdc genes). Remarkably, all proteins of the sex-specific Dpy and Sdc classes interact and form a single complex, the DC complex (DCC). Structurally, the DCC is similar to condensin I and loaded on the X chromosome at rex (recruitment element on X) sites characterized by a 12-base-pair (bp) MEX (motif enriched on X) consensus sequence (Ercan et al. 2009;Jans et al. 2009). Thirty-eight rex sites have been experimentally demonstrated, and sequence analysis suggests the presence of 100-300 sites on the X chromosome (Jans et al. 2009). This estimation is due to the fact that the DCC moves and spreads along the X chromosome from its nucleation sites (Csankovszki et al. 2004). The DCC accumulates at promoters upstream of transcription start sites; however, the relationship between DCC accumulation and transcriptional regulation remains disputed (Ercan et al. 2009;Jans et al. 2009). Genome-wide run-on experiments have shown that the DCC reduces transcription from the X chromosome, although RNA polymerase chromatin immunoprecipitation (ChIP) does not show a significant reduction compared with autosomes (Kruesi et al. 2013). How DCC loading regulates RNA polymerase II (Pol II) function still remains unknown. Compared with autosomes, compensated X chromatin is depleted for the histone variant HTZ-1 and H4K16 acetylation, likely a consequence of lower transcription, and carries high H4K20 monomethylation (H4K20me1), spreading with the DCC (Whittle et al. 2008;Petty et al. 2011;Vielle et al. 2012;Wells et al. 2012). Inside the nuclear space, the compensated X displays a peculiar tridimensional conformation: While all autosomes have high int...

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“…In both yeast and human, TPE involves chromatin modifications (acetylation, methylation) (Smith et al 2000;Zhou et al 2011;Weuts et al 2012;Buxton et al 2014) and chromatin remodeling factors such as SIRT6 (Tennen et al 2011;Anderson et al 2014). TPE has also been implicated with telomere length changes and telomere-associated proteins (Blackburn 2001;Weuts et al 2012;Ferreira et al 2013). In FSHD, telomere length influences expression of DUX4 and FRG2 (FSHD region gene 2) (Stadler et al 2013), suggesting that this region is sensitive to TPE.…”

Section: [Supplemental Materials Is Available For This Article]mentioning

confidence: 99%

SORBS2transcription is activated by telomere position effect–over long distance upon telomere shortening in muscle cells from patients with facioscapulohumeral dystrophy

et al. 2015

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DNA is organized into complex three-dimensional chromatin structures, but how this spatial organization regulates gene expression remains a central question. These DNA/chromatin looping structures can range in size from 10-20 kb (enhancers/repressors) to many megabases during intra-and inter-chromosomal interactions. Recently, the influence of telomere length on chromatin organization prior to senescence has revealed the existence of long-distance chromatin loops that dictate the expression of genes located up to 10 Mb from the telomeres (Telomere Position Effect-Over Long Distances [TPE-OLD]). Here, we demonstrate the existence of a telomere loop at the 4q35 locus involving the sorbin and SH3 domain-containing protein 2 gene, SORBS2, a skeletal muscle protein using a modification of the chromosome conformation capture method. The loop reveals a cis-acting mechanism modifying SORBS2 transcription. The expression of this gene is altered by TPE-OLD in myoblasts from patients affected with the age-associated genetic disease, facioscapulohumeral muscular dystrophy (FSHD1A, MIM 158900). SORBS2 is expressed in FSHD myoblasts with short telomeres, while not detectable in FSHD myoblasts with long telomeres or in healthy myoblasts regardless of telomere length. This indicates that TPE-OLD may modify the regulation of the 4q35 locus in a pathogenic context. Upon differentiation, both FSHD and healthy myotubes express SORBS2, suggesting that SORBS2 is normally up-regulated by maturation/differentiation of skeletal muscle and is misregulated by TPE-OLD-dependent variegation in FSHD myoblasts. These findings provide additional insights for the complexity and age-related symptoms of FSHD.

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The shelterin protein POT-1 anchors Caenorhabditis elegans telomeres through SUN-1 at the nuclear periphery

Abstract: Telomere positioning near the nuclear envelope during Caenorhabditis elegans development requires the nuclear envelope protein SUN-1, the Shelterin component POT-1, and the SUMO ligase GEI-17.

Cited by 45 publications

References 47 publications

Cell Biology of theCaenorhabditis elegansNucleus

Cell Biology of theCaenorhabditis elegansNucleus

Differential spatial and structural organization of the X chromosome underlies dosage compensation in C. elegans

SORBS2transcription is activated by telomere position effect–over long distance upon telomere shortening in muscle cells from patients with facioscapulohumeral dystrophy

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