The Role of CTCF in the Organization of the Centromeric 11p15 Imprinted Domain Interactome
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PROVIDER: PRJNA723928 | ENA |
REPOSITORIES: ENA
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Project description:The Role of CTCF in the Organization of the Centromeric 11p15 Imprinted Domain Interactome
| PRJNA723927 | ENA
Project description:DNA methylation, chromatin-binding proteins, and DNA looping are common components regulating genomic imprinting which leads to parent-specific monoallelic gene expression. Loss of methylation (LOM) at the human imprinting center 2 (IC2) on chromosome 11p15 is the most common cause of the imprinting overgrowth disorder Beckwith-Wiedemann Syndrome (BWS). Here, we report a familial transmission of a 7.6 kB deletion that ablates the core promoter of KCNQ1. This structural alteration leads to IC2 LOM and causes recurrent BWS. We find that occupancy of the chromatin organizer CTCF is disrupted proximal to the deletion, which causes chromatin architecture changes both in cis and in trans. We also profile the chromatin architecture of IC2 in patients with sporadic BWS caused by isolated LOM to identify conserved features of IC2 regulatory disruption. A strong interaction between CTCF sites around KCNQ1 and CDKN1C likely drive their expression on the maternal allele, while a weaker interaction involving the imprinting control region element may impede this connection and mediate gene silencing on the paternal allele. We present an imprinting model in which KCNQ1 transcription is necessary for appropriate CTCF binding and a novel chromatin conformation to drive allele-specific gene expression.
| S-EPMC8216465 | biostudies-literature
Project description:Inborn defects in DNA repairare associated with complex developmental disorders whose causal mechanisms are poorly understood. Using an in vivo biotinylation tagging approach in mice, we show that the nucleotide excision repair (NER) structure-specific endonuclease ERCC1-XPF complex interacts with the insulator binding protein CTCF, the cohesin subunits SMC1A and SMC3 and with MBD2; the factors co-localize with ATRX at the promoters and control regions (ICRs) of imprinted genes during postnatal hepatic development. Loss of Ercc1or exposure to mitomycin C triggers the localization of CTCF to heterochromatin, the dissociation of the CTCF-cohesin complex and ATRXfrom promoters and ICRs,altered histone marks and the aberrant developmental expression of imprinted genes without altering DNA methylation. We propose that ERCC1-XPF cooperates with CTCF and the cohesinto facilitatet he developmental silencing of imprinted genes and that persistent DNA damage triggers chromatin changes that affect gene expression programs associated with NER disorders.
2017-04-04 | PXD005897 | Pride
Project description:The centromere is the genetic locus that organizes the proteinaceous kinetochore and is responsible for attachment of the chromosome to the spindle at mitosis and meiosis. In most eukaryotes, the centromere consists of highly repetitive DNA sequences that are occupied by nucleosomes containing the CenH3 histone variant, whereas in budding yeast, an ~120-bp Centromere DNA Element (CDE) that is sufficient for centromere function is occupied by a single right-handed CenH3 (Cse4) nucleosome. However, these in vivo observations are inconsistent with in vitro evidence for left-handed octameric CenH3 nucleosomes. To help resolve these inconsistencies, we characterized yeast centromeric chromatin at single base-pair resolution. Intact particles containing both Cse4 and H2A are precisely protected from micrococcal nuclease over the entire CDE of all 16 yeast centromeres in both solubilized chromatin and the insoluble kinetochore. Small DNA-binding proteins protect CDEI and CDEIII and delimit the centromeric nucleosome to the ~80-bp CDEII, only enough for a single DNA wrap. As expected for a tripartite organization of centromeric chromatin, loss of Cbf1 protein, which binds to CDEI, both reduces the size of the centromere-protected region and shifts its location towards CDEIII. Surprisingly, Cse4 overproduction caused genome-wide misincorporation of non-functional CenH3-containing nucleosomes that protect ~135 base pairs and are preferentially enriched at sites of high nucleosome turnover. Our detection of two forms of CenH3 nucleosomes in the yeast genome, a singly wrapped particle at the functional centromere and octamer-sized particles on chromosome arms, reconcile seemingly conflicting in vivo and in vitro observations. We used micrococcal nuclease mapping, chromatin immunoprecipitation and paired-end sequencing to determine the structure of yeast centromeres at single base-pair resolution.
2011-12-07 | E-GEOD-28298 | biostudies-arrayexpress
Project description:The centromere is the genetic locus that organizes the proteinaceous kinetochore and is responsible for attachment of the chromosome to the spindle at mitosis and meiosis. In most eukaryotes, the centromere consists of highly repetitive DNA sequences that are occupied by nucleosomes containing the CenH3 histone variant, whereas in budding yeast, an ~120-bp Centromere DNA Element (CDE) that is sufficient for centromere function is occupied by a single right-handed CenH3 (Cse4) nucleosome. However, these in vivo observations are inconsistent with in vitro evidence for left-handed octameric CenH3 nucleosomes. To help resolve these inconsistencies, we characterized yeast centromeric chromatin at single base-pair resolution. Intact particles containing both Cse4 and H2A are precisely protected from micrococcal nuclease over the entire CDE of all 16 yeast centromeres in both solubilized chromatin and the insoluble kinetochore. Small DNA-binding proteins protect CDEI and CDEIII and delimit the centromeric nucleosome to the ~80-bp CDEII, only enough for a single DNA wrap. As expected for a tripartite organization of centromeric chromatin, loss of Cbf1 protein, which binds to CDEI, both reduces the size of the centromere-protected region and shifts its location towards CDEIII. Surprisingly, Cse4 overproduction caused genome-wide misincorporation of non-functional CenH3-containing nucleosomes that protect ~135 base pairs and are preferentially enriched at sites of high nucleosome turnover. Our detection of two forms of CenH3 nucleosomes in the yeast genome, a singly wrapped particle at the functional centromere and octamer-sized particles on chromosome arms, reconcile seemingly conflicting in vivo and in vitro observations.
2011-12-07 | GSE28298 | GEO
Project description:The role of CTCF in stabilizing long-range interactions between chromatin sites essential for maintaining nuclear architecture is well established. Most of these interactions involve recruitment of the cohesin complex to chromatin via CTCF. We find that CTCF also interacts with the centromeric protein CENP-E both in vitro and in vivo. We identified CTCF sites in pericentric/centromeric DNA and found that, early in mitosis, CTCF binds and recruits CENP-E to these sites. Unlike most known CTCF genomic sites, the CTCF-binding sites in the pericentric/centromeric regions interact strongly with the C-terminal fingers of CTCF. Overexpression of a small CENP-E fragment, targeted to these CTCF sites, results in a delay in alignment of some chromosomes during mitosis, suggesting that the recruitment of CENP-E by CTCF is physiologically important. We conclude that CTCF helps recruit CENP-E to the centromere during mitosis and that it may do so through a structure stabilized by the CTCF/CENP-E complex.
| S-EPMC4633288 | biostudies-literature
Project description:Centromeric chromatin in Koala
| PRJNA436016 | ENA
Project description:In human cells chromosome specific aneuploidy was measured. Then, using NGS methods, centromeric features were measured for each chromosome (including centromere length and amount of centromeric proteins). The study aims at testing an association between centromeric features and missegregation rate.
2019-11-26 | GSE132193 | GEO
Project description:CTCF is a master regulator that plays a role in genome architecture and gene expression. A key aspect of CTCF’s mechanism involves bringing together distant genetic elements for intra- and inter-chromosomal interactions. Evidence from epigenetic processes, such as X-chromosome inactivation (XCI), suggests that CTCF may carry out its functions through interacting RNAs. Using genome-wide approaches to investigate the relationship between CTCF’s RNA interactome and its epigenomic landscape, here we report that CTCF interacts with thousands of transcripts in mouse embryonic stem cells (mESC), many in close proximity to CTCF’s genomic binding sites. Biochemical analysis demonstrates that CTCF is a high-affinity RNA binding protein that contacts RNA directly and specifically. In the XCI model, CTCF binds the active and inactive X-chromosomes allele-specifically. At the X-inactivation center, Tsix RNA binds CTCF and targets CTCF to a region associated with X-chromosome pairing. Our work implicates CTCF-RNA interactions in long-range chromosomal interactions in trans and adds a new layer of complexity to CTCF regulation. The genome-wide datasets reported here will provide a useful resource for further study of CTCF-mediated epigenomic regulation. CTCF RNA interactome was identified by UV-crosslinking and immunoprecipitation followed by high-throughput sequencing (CLIP-seq), and was compared to CTCF's epigenomic landscape as obtained by chromatin immunoprecipitation (ChIP-seq).
2015-01-09 | E-GEOD-58242 | biostudies-arrayexpress
Project description:We report high throughput sequencing of DNA associated with centromeric chromatin in the koala genome.
2018-04-26 | GSE111153 | GEO