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Expanding heterochromatin reveals discrete subtelomeric domains delimited by chromatin landscape transitions

ABSTRACT: Expanding heterochromatin reveals discrete subtelomeric domains delimited by chromatin landscape transitions

PROVIDER: PRJNA417053 | ENA |

REPOSITORIES: ENA

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Expanding heterochromatin reveals discrete subtelomeric domains delimited by chromatin landscape transitions

Project description:The eukaryotic genome is divided into chromosomal domains of heterochromatin and euchromatin. Transcriptionally silent heterochromatin is found at subtelomeric regions, leading to the telomeric position effect (TPE) in yeast, fly and man. Heterochromatin generally initiates and spreads from defined loci, and diverse mechanisms prevent the ectopic spread of heterochromatin into euchromatin. Here, we overexpressed the silencing factor Sir3 at various levels in yeast, and found that Sir3 spreading into Extended Silent Domains (ESD) eventually reached saturation at subtelomeres. We observed that Sir3 spreading into ESDs covered zone associated with specific histone marks in wild-type cells and stopped at zones of histone mark transitions including H3K79 tri-methylation levels. The conserved enzyme Dot1 deposits H3K79 methylation, and we found that it is essential for viability upon overexpression of Sir3, but not of a spreading-defective mutant Sir3A2Q. These data suggest that H3K79 methylation actively blocks Sir3 spreading. Lastly, we demonstrate that our work uncovers previously uncharacterized discrete subtelomeric domains associated with specific chromatin features, that offers a new viewpoint on how to separate subtelomeres from the core chromosome.

2018-10-08 | GSE106499 | GEO

Expanding heterochromatin reveals discrete subtelomeric domains delimited by chromatin landscape transitions.

Project description: Not available

| S-EPMC6280759 | biostudies-literature

Dose-dependency of heterochromatin domains reveals subtelomeric structuration in budding yeast

Project description:The eukaryotic genome is divided into chromosomal domains of distinct gene activities. Transcriptionally silent chromatin is found in subtelomeric regions leading to telomeric position effect (TPE) in yeast, fly and man. Silent chromatin generally initiates at defined loci and tends to propagate from those sites by self-recruitment mechanisms implying the requirement for processes preventing ectopic spreading of silencing. Barrier elements that can block the spread of silent chromatin have been documented, but their relative efficiency is not known. Here we explore the dose-dependency of silencing factors for the extent of TPE in budding yeast. We characterized genome wide the impact of overexpressing the silencing factors Sir2 and Sir3 on the spreading of Sir3 and its impact on coding and non-coding transcription. We thus reveal that extension of silent domains can reach saturation. Analysis of published data sets enabled to uncover that the extension of Sir3 bound domains stops at zones corresponding to transitions of specific histone marks including H3K79 methylation that is deposited by the conserved enzyme Dot1. Importantly, DOT1 is essential for viability when Sir3 is in excess indicating that this transition actively blocks Sir3 spreading. Our work uncovers previously uncharacterized discrete chromosomal domains associated with specific chromatin features and demonstrates that TPE is efficiently restricted to subtelomeres by the preexisting chromatin landscape.

2018-10-15 | GSE104391 | GEO

Dose-dependency of heterochromatin domains reveals subtelomeric structuration in budding yeast

Project description:Dose-dependency of heterochromatin domains reveals subtelomeric structuration in budding yeast

| PRJNA412516 | ENA

Dynamics of embryonic stem cell differentiation inferred from single-cell transcriptomics show a series of transitions through discrete cell states

Project description:Using a statistical framework to analyze single-cell transcriptomics data, we infer the gene expression dynamics of early mouse embryonic stem (mES) cell differentiation, uncovering discrete transitions across nine cell states. We validate the predicted transitions across discrete states using flow cytometry. Moreover, using live-cell microscopy, we show that individual cells undergo abrupt transitions from a naïve to primed pluripotent state. Using the inferred discrete cell states to build a probabilistic model for the underlying gene regulatory network, we further predict and experimentally verify that these states have unique response to perturbations, thus defining them functionally.

2017-10-17 | GSE105054 | GEO

Neurospora crassa genome organization requires subtelomeric facultative heterochromatin

Project description:Facultative heterochromatin in the filamentous fungus Neurospora crassa is identified by the repressive histone mark H3K27me3 and is primarily subtelomeric, while constitutive heterochromatin, marked by the DIM-5-catalzyed H3K9me3, is found at centromeres, telomeres, and smaller dispersed regions. In strains lacking constitutive heterochromatin (e.g., Δdim-5), H3K27me2/3 relocalizes to the regions formerly marked by H3K9me3. H3K27me3 is catalyzed by the SET-7 histone methyltransferase subunit of the Polycomb Repressive Complex 2 (PRC2); another PRC2 member, Neurospora p55 (NPF) regulates subtelomeric H3K27me2/3. Despite the de-repression of >70 genes, a Δset-7 strain has no distinguishable phenotype. To investigate the facultative heterochromatin contribution to genome organization, we performed high-throughput “chromosome conformation capture” (Hi-C) on mutants with impacted H3K27me2/3 deposition. A Δset-7 strain has decreased inter-/intra-subtelomeric contacts among others; this pattern is mirrored in a Δnpf strain, which lacks subtelomeric H3K27me3. In a Δset-7 strain, telomere bundles were often uncoupled from the nuclear membrane and de-repressed genes were subtelomeric. The chromosome conformation of a Δset-7;Δdim-5 double mutant was similar to Δset-7, suggesting that facultative heterochromatin relocalization does not compensate for H3K9me3 loss and rescue the Neurospora genome organization in strains with defective constitutive heterochromatin.

2016-10-27 | GSE82222 | GEO

The FUN30 Chromatin Remodeler Fft3 Protects Centromeric and Subtelomeric Domains from Euchromatin Formation

Project description:The chromosomes of eukaryotes are organized into structurally and functionally discrete domains. This implies the presence of insulator elements that separate adjacent domains, allowing them to maintain different chromatin structures. We show that the Fun30 chromatin remodeler, Fft3, is essential for maintaining a proper chromatin structure at centromeres and subtelomeres. Fft3 is localized to insulator elements and inhibits euchromatin assembly in silent chromatin domains. In its absence, euchromatic histone modifications and histone variants invade centromeres and subtelomeres, causing a mis-regulation of gene expression and severe chromosome segregation defects. Our data strongly suggest that Fft3 controls the identity of chromatin domains by protecting these regions from euchromatin assembly.

2011-04-02 | E-MEXP-3044 | biostudies-arrayexpress

GTP-dependent regulation of heterochromatin fluctuations at subtelomeric regions in S. cerevisiae

Project description:Analysis of gene expression changes following deletion of SIR genes at subtelomeric region. A total of 4 samples were analyzed : Wild type (BY4742) strain, SIR2 deletion strain, SIR3 deletion strain, SIR4 deletion strain.

2023-12-28 | GSE230739 | GEO

Discrete genomic domains exhibit co-occurrence of H3K9me3 and H3K27me3 histone modifications throughout Drosophila

Project description:Full title: Discrete genomic domains exhibit co-occurrence of H3K9me3 and H3K27me3 histone modifications throughout Drosophila development Trimethylation of histone H3 on lysine 9 (H3K9me3) and lysine 27 (H3K27me3) is strongly associated with gene silencing and transcriptional repression in both Drosophila and mammals. H3K9me3 is linked to the formation of heterochromatin, while H3K27me3 is a hallmark of repression of euchromatic genes by Polycomb group proteins. We examined the genomic distribution of the two modifications at high resolution over nine different stages of Drosophila development, and found that they are present in large overlapping domains in euchromatin. These dual-mark domains are stable throughout the life of the fly, and cover genomic regions greatly enriched in developmental regulatory genes with spatially restricted expression. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf

2009-10-16 | GSE18572 | GEO

Telomere shortening is associated with over-expression of subtelomeric genesin thyroid tumors.

Project description:To determine whether telomere shortening in thyroid tumors delineates gene expression of subtelomeric regions, we performed RNA sequencing in a set of tumors (n = 15) and compare gene expression profiles of subtelomeric and non-subtelomeric genes between short telomere tumors and normal telomere tumors. We defined as subtelomeric genes, those located within the 5 megabase windows (Mb) adjacent to the telomeres.

2022-08-24 | GSE193623 | GEO

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