Defining the landscape of chromatin-associated RNAs at human centromeric repeats
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE298896 | GEO | 2025/06/10
REPOSITORIES: GEO
Similar Datasets
Project description:The centromere is a defining feature of eukaryotic chromosomes and is essential for the segregation of chromosomes during cell division. Centromeres are universally marked by the histone variant cenH3 and are restricted to specialized chromatin that most commonly localized to a single position along the chromosome. However, the DNA on which centromeric nucleosomes assemble is not conserved and varies greatly in size and composition. It ranges from genetically defined point centromeres that assemble a single cenH3-containing nucleosome to epigenetically defined regional centromeres embedded in megabases of tandemly repeated DNA to holocentromeres that extend along the length of the entire chromosomes. The organization of regional and holocentric centromeres has so far been elusive, as the precise locations of cenH3-containing sequences could not be determined. Our results show that the point centromere is the basic unit of holocentromeres and provide a basis for understanding how centromeric chromatin is maintained. We use high-resolution mapping of cenH3-associated DNA to show that Caenorhabditids elegans holocentromeres are organized as dispersed but discretely localized point centromeres.
2014-04-08 | E-GEOD-44412 | biostudies-arrayexpress
Project description:The focal attachment of the kinetochore to the centromere core is essential for genome maintenance, yet the highly repetitive nature of human centromeres limits our understanding of their chromatin organization. We demonstrate that single-molecule chromatin fiber sequencing can uniquely resolve chromatin organization within centromeres at single-molecule and single-nucleotide resolution. We find that the centromere core contains a dichotomous chromatin organization not found elsewhere in the genome, which is characterized by highly accessible chromatin patches heterogeneously punctuated amongst tightly compacted nucleosome arrays. These highly accessible chromatin patches correspond to sites of kinetochore attachment, and clustered CENP-B occupancy within these patches phase nucleosome arrays to the alpha-satellite repeat. This dichotomous chromatin organization is conserved between humans despite the marked divergence of the underlying alpha-satellite organization and is similarly conserved in primate centromeres that lack alpha-satellite repeats, indicating that functional conservation within centromeres is mediated at the level of chromatin, not DNA.
2023-08-02 | GSE226394 | GEO
Project description:In organisms ranging from vertebrates to plants, major components of centromeres are rapidly-evolving repeat sequences, such as tandem repeats (TRs) and transposable elements (TEs). These repeats harbor centromere-specific histone H3 (CENH3), which also evolves rapidly. Complete centromere structures recently determined in human and Arabidopsis suggest frequent integration and purging of retrotransposons within the TR regions of centromeres. Despite the high impact of “centrophilic” retrotransposons on the paradox of rapid centromere evolution, the mechanisms involved in centromere targeting remain poorly understood in any organism. Here we show that both Ty3 and Ty1/Copia LTR elements rapidly turnover within the centromeric TRs of Arabidopsis species. We demonstrate that the Ty1/Copia element Tal1 (Transposon of Arabidopsis lyrata 1) integrates de novo into regions occupied by CENH3 in A. thaliana, and that ectopic expansion of the CENH3 region results in spread of Tal1 integration regions. The integration spectra of chimeric TEs revealed the key structural variations responsible for the contrasting chromatin targeting specificities to centromeres versus gene-rich regions, which have recurrently converted during the evolution of these TEs. Our findings reveal the impact of centromeric chromatin on TE-mediated rapid centromere evolution, with relevance across eukaryotic genomes.
2024-08-08 | GSE263225 | GEO
Project description:In organisms ranging from vertebrates to plants, major components of centromeres are rapidly-evolving repeat sequences, such as tandem repeats (TRs) and transposable elements (TEs). These repeats harbor centromere-specific histone H3 (CENH3), which also evolves rapidly. Complete centromere structures recently determined in human and Arabidopsis suggest frequent integration and purging of retrotransposons within the TR regions of centromeres. Despite the high impact of “centrophilic” retrotransposons on the paradox of rapid centromere evolution, the mechanisms involved in centromere targeting remain poorly understood in any organism. Here we show that both Ty3 and Ty1/Copia LTR elements rapidly turnover within the centromeric TRs of Arabidopsis species. We demonstrate that the Ty1/Copia element Tal1 (Transposon of Arabidopsis lyrata 1) integrates de novo into regions occupied by CENH3 in A. thaliana, and that ectopic expansion of the CENH3 region results in spread of Tal1 integration regions. The integration spectra of chimeric TEs revealed the key structural variations responsible for the contrasting chromatin targeting specificities to centromeres versus gene-rich regions, which have recurrently converted during the evolution of these TEs. Our findings reveal the impact of centromeric chromatin on TE-mediated rapid centromere evolution, with relevance across eukaryotic genomes.
2024-08-08 | GSE263224 | GEO
Project description:Centromeres are maintained epigenetically by the presence of CENP-A, an evolutionarily-conserved histone H3 variant, which directs kinetochore assembly and hence, centromere function. To identify factors that promote assembly of CENP-A chromatin, we affinity selected solubilised fission yeast CENP-ACnp1 chromatin. All subunits of the Ino80 complex were enriched, including the auxiliary subunit Hap2. In addition to a role in maintenance of CENP-ACnp1 chromatin integrity at endogenous centromeres, Hap2 is required for de novo assembly of CENP-ACnp1 chromatin on naïve centromere DNA and promotes H3 turnover on centromere regions and other loci prone to CENP-ACnp1 deposition. Prior to CENP-ACnp1 chromatin assembly, Hap2 is required for transcription from centromere DNA. These analyses suggest that Hap2-Ino80 destabilises H3 nucleosomes on centromere DNA through transcription-mediated histone H3 turnover, driving the replacement of resident H3 nucleosomes with CENP-ACnp1 nucleosomes. These inherent properties define centromere DNA by directing a program that mediates CENP-ACnp1 assembly on appropriate sequences.
2020-05-27 | PXD016602 | Pride
Project description:The centromere is a defining feature of eukaryotic chromosomes and is essential for the segregation of chromosomes during cell division. Centromeres are universally marked by the histone variant cenH3 and are restricted to specialized chromatin that most commonly localized to a single position along the chromosome. However, the DNA on which centromeric nucleosomes assemble is not conserved and varies greatly in size and composition. It ranges from genetically defined point centromeres that assemble a single cenH3-containing nucleosome to epigenetically defined regional centromeres embedded in megabases of tandemly repeated DNA to holocentromeres that extend along the length of the entire chromosomes. The organization of regional and holocentric centromeres has so far been elusive, as the precise locations of cenH3-containing sequences could not be determined. Our results show that the point centromere is the basic unit of holocentromeres and provide a basis for understanding how centromeric chromatin is maintained.
2014-04-08 | GSE44412 | GEO
Project description:The centromere is the chromosomal site for assembly of the kinetochore where spindle fibers attach during cell division. In most muticellular eukaryotes, centromeres are composed of long tracks of satellite repeats that are recalcitrant to sequencing and fine scale genetic mapping. Here we report the genomic and genetic characterization of the complete centromere of rice chromosome 3. Using a DNA fiber-fluorescence in situ hybridization approach, we demonstrated that the centromere of chromosome 3 (Cen3) contains ~414 kb of the centromeric satellite repeat CentO. Cen3 includes a ~1,851-kb domain associated with CENH3, the centromere-specific histone H3 variant. This CENH3-associated chromatin domain is embedded within a 3,083-kb region that lacks genetic recombination. We detected several active genes within the CENH3-binding domain based on a comprehensive annotation and a survey for matches with mRNA signatures. However, the gene density in the CENH3-binding domain is significantly lower than in the pericentromeric domains. In contrast, the CENH3-binding domain contains a higher percentage of repetitive DNA sequences than the pericentromeric regions. These results suggest that Cen3 is in the process of evolving from a genic region toward an accumulation of satellite repeats and transposable elements that is more characteristic of centromeres in most complex eukaryotic species. MPSS was performed to sequence small RNAs that derived from inflorescence and seedling. The method for the MPSS sequencing of small RNAs are described in the paper associated with this dataset (Lu et al., 2005).
2006-05-26 | E-GEOD-4912 | biostudies-arrayexpress
Project description:Centromeres play an essential role in cell division by specifying the site of kinetochore formation on each chromosome so that chromosomes can attach to the mitotic spindle for segregation. Centromeres are defined epigenetically by the histone H3 variant CEntromere Protein A (CENP-A). Dividing cells maintain the centromere by depositing new CENP-A each cell cycle to replenish CENP-A diluted by replication. The CENP-A nucleosome serves as the primary signal to the machinery responsible for its replenishment. Vertebrate centromeres are frequently built on repetitive sequences organized in tandem arrays. Repetitive centromeric DNA has been suggested to play a role in centromere maintenance and in de novo centromere formation, but this has been difficult to dissect because of the difficulty in manipulating centromere in cells. Extracts from Xenopus laevis eggs are able to assemble centromeres and kinetochores in vitro and thus provide a useful system for studying the role of centromeric DNA in centromere formation. However centromeric sequences in X. laevis have not been extensively characterized.. In this study we characterize repeat sequences found at X. laevis centromeres. We utilize a k-mer based approach in order to uncover the previously unknown diversity of X. laevis centromeric sequences. We validate centromere localization of repeat sequences by in situ hybridization and identify the location of the centromeric repetitive array on each chromosome by mapping the distribution of centromere enriched k-mers on the Xenopus genome. Our identification of X. laevis centromere sequences enables previously unapproachable genomic studies of centromeres. The k-mer based approach that we used to investigate centromeric repetitive DNA is suitable for the analysis of other repetitive sequences found across the genome or the study of repeats in other organisms.
2020-06-24 | GSE153058 | GEO
Project description:De novo centromeres originate occasionally from non-centromeric regions of chromosomes, providing an excellent model system to study centromeric chromatin. The maize mini-chromosome Dp3a contains a de novo centromere, which was derived from a euchromatic site on the long arm of chromosome 3 that lacks traditional centromeric repeat sequences. Our previous study found that the CENH3 binding domain of this de novo centromere is only 350 kb with a high-density gene distribution with low-density of transposons. Here we analyzed the kinetochore complex assembled on the de novo centromere, which revealed that it resembles the native centromeres. Meiotic analyses showed that the Dp3a mini-chromosome formed bi-orientation during meiosis I and could stably transmit through meiosis. We applied next generation sequencing technology to analyze gene transcription, DNA methylation and histone modifications for this region. Our RNA-seq data revealed that active chromatin is not a barrier for de novo centromere formation. The gene expression level within the Dp3a breakpoints of native chromosome 3 indicated a gene dosage effect due to the additional copy of Dp3a mini-chromosome region in chromosome 3. Bisulfite-ChIP-seq results indicate a slightly increased DNA methylation level after de novo centromere formation, reaching the level of a native centromere. No strand-specific bias of DNA methylation was found at maize native and Dp3a de novo centromeres. H2A-T133 phosphorylation occurs in the CENH3 nucleosome. These results provide insight into the mechanism of de novo centromere formation and subsequent consequences.
2016-12-01 | GSE64641 | GEO
Project description:The centromere is the chromosomal site for assembly of the kinetochore where spindle fibers attach during cell division. In most muticellular eukaryotes, centromeres are composed of long tracks of satellite repeats that are recalcitrant to sequencing and fine scale genetic mapping. Here we report the genomic and genetic characterization of the complete centromere of rice chromosome 3. Using a DNA fiber-fluorescence in situ hybridization approach, we demonstrated that the centromere of chromosome 3 (Cen3) contains ~414 kb of the centromeric satellite repeat CentO. Cen3 includes a ~1,851-kb domain associated with CENH3, the centromere-specific histone H3 variant. This CENH3-associated chromatin domain is embedded within a 3,083-kb region that lacks genetic recombination. We detected several active genes within the CENH3-binding domain based on a comprehensive annotation and a survey for matches with mRNA signatures. However, the gene density in the CENH3-binding domain is significantly lower than in the pericentromeric domains. In contrast, the CENH3-binding domain contains a higher percentage of repetitive DNA sequences than the pericentromeric regions. These results suggest that Cen3 is in the process of evolving from a genic region toward an accumulation of satellite repeats and transposable elements that is more characteristic of centromeres in most complex eukaryotic species. MPSS was performed to sequence small RNAs that derived from 16 untreated and 6 abiotic-treated diverse tissue libraries. The method for the MPSS sequencing of mRNAs is described in Brenner et al. (Nat Biotechnol. 2000 18:630).
2006-05-26 | E-GEOD-4920 | biostudies-arrayexpress