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Genome-wide maps of RAP1 binding sites.

ABSTRACT: By performing chromatin immunoprecipitation coupled with ultra-high-throughput sequencing (ChIP-seq), we find that RAP1 binds to telomeres as well as to extra-telomeric sites through the (TTAGGG)2 consensus motif. Extra-telomeric RAP1 binding sites are particularly abundant at subtelomeric regions, and this is in agreement with preferential deregulation of subtelomeric genes in Rap1-deficient cells. Significantly, more than 70% of extratelomeric RAP1 binding sites are located in the vicinity of known genes and about 40% of the genes deregulated in Rap1-null cells contain binding sites for RAP1, suggesting a role of RAP1 in transcriptional control. Examination of RAP1 binding by CHIP-seq in two independent wild-type mefs using as negative control two independent RAP1-deleted mefs

ORGANISM(S): Mus musculus

SUBMITTER: Paula Martinez

PROVIDER: E-GEOD-20867 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Mammalian Rap1 controls telomere function and gene expression through binding to telomeric and extratelomeric sites.

Martinez Paula P Thanasoula Maria M Carlos Ana R AR Gómez-López Gonzalo G Tejera Agueda M AM Schoeftner Stefan S Dominguez Orlando O Pisano David G DG Tarsounas Madalena M Blasco Maria A MA

Nature cell biology 20100711 8

Rap1 is a component of the shelterin complex at mammalian telomeres, but its in vivo role in telomere biology has remained largely unknown to date. Here we show that Rap1 deficiency is dispensable for telomere capping but leads to increased telomere recombination and fragility. We generated cells and mice deleted for Rap1; mice with Rap1 deletion in stratified epithelia were viable but had shorter telomeres and developed skin hyperpigmentation in adulthood. By performing chromatin immunoprecipit ...[more]

PMID: 20622869

Similar Datasets

Genome-wide maps of RAP1 binding sites.

Project description:By performing chromatin immunoprecipitation coupled with ultra-high-throughput sequencing (ChIP-seq), we find that RAP1 binds to telomeres as well as to extra-telomeric sites through the (TTAGGG)2 consensus motif. Extra-telomeric RAP1 binding sites are particularly abundant at subtelomeric regions, and this is in agreement with preferential deregulation of subtelomeric genes in Rap1-deficient cells. Significantly, more than 70% of extratelomeric RAP1 binding sites are located in the vicinity of known genes and about 40% of the genes deregulated in Rap1-null cells contain binding sites for RAP1, suggesting a role of RAP1 in transcriptional control.

2010-07-10 | GSE20867 | GEO

Genome-wide distribution of AdpA, a global regulator for secondary metabolism and morphological differentiation in Streptomyces [liquid]

Project description:AdpA is a global transcriptional activator triggering morphological differentiation and secondary metabolism in Streptomyces griseus. AdpA influences expression of >1,000 genes, but the overall picture of AdpA regulon has been obscure. Here, we took snapshots of distribution of AdpA across the chromosome in living S. griseus cells by ChIP/ChAP-seq analysis. In both liquid and solid cultures, AdpA bound to similar >1,200 sites, which were located on not only putative regulatory regions (65 %) but also regions (35 %) that appeared not to affect transcription. Transcriptome analysis indicated that approximately 40% of the AdpA binding sites in putative regulatory regions were involved in gene regulation. AdpA was indicated to act as a transcriptional repressor as well as an activator. Expression profiles of AdpA-target genes were very different between liquid and solid cultures in spite of similar AdpA-binding profiles. We therefore concluded that AdpA directly controls >500 genes in cooperation with other regulatory proteins in many cases. In vitro AdpA binding to the selected 304 AdpA-binding sites was examined, revealing several unique characteristics of AdpA regarding its DNA-binding property. This study gave the first experimental insight into the extent of AdpA regulon, indicating many genes under the direct control of AdpA. Analysis of genome-wide distribution of AdpA on liquid culture with two different methods to isolate AdpA-DNA complex

2012-04-03 | E-GEOD-34036 | biostudies-arrayexpress

Genome-wide distribution of AdpA, a global regulator for secondary metabolism and morphological differentiation in Streptomyces [solid]

Project description:AdpA is a global transcriptional activator triggering morphological differentiation and secondary metabolism in Streptomyces griseus. AdpA influences expression of >1,000 genes, but the overall picture of AdpA regulon has been obscure. Here, we took snapshots of distribution of AdpA across the chromosome in living S. griseus cells by ChIP/ChAP-seq analysis. In both liquid and solid cultures, AdpA bound to similar >1,200 sites, which were located on not only putative regulatory regions (65 %) but also regions (35 %) that appeared not to affect transcription. Transcriptome analysis indicated that approximately 40% of the AdpA binding sites in putative regulatory regions were involved in gene regulation. AdpA was indicated to act as a transcriptional repressor as well as an activator. Expression profiles of AdpA-target genes were very different between liquid and solid cultures in spite of similar AdpA-binding profiles. We therefore concluded that AdpA directly controls >500 genes in cooperation with other regulatory proteins in many cases. In vitro AdpA binding to the selected 304 AdpA-binding sites was examined, revealing several unique characteristics of AdpA regarding its DNA-binding property. This study gave the first experimental insight into the extent of AdpA regulon, indicating many genes under the direct control of AdpA. Time course analysis of genome-wide distribution of AdpA on solid culture

2012-04-03 | E-GEOD-34037 | biostudies-arrayexpress

Non-telomeric role for Rap1 in regulating metabolism and protecting against obesity

Project description:The mammalian telomere-binding protein Rap1 was found to have additional non-telomeric functions, acting as a transcriptional cofactor and a regulator of the NF-kB pathway. Here, we assess the effect of disrupting mouse Rap1 in vivo, and report on its unanticipated role in metabolic regulation and body weight homeostasis. Rap1 inhibition causes dysregulation in hepatic as well as adipose function. In addition, using a separation-of-function allele, we show that the metabolic function of Rap1 is independent of its recruitment to TTAGGG binding elements found at telomeres, and at other interstitial loci. We have utilized microarrays to outline gene expression changes resulting from Rap1-deficiency when compared to the wild-type controls. Total RNA was isolated from the liver and intra-abdominal white adipose tissue of 3 female Rap1 deficient mice and 3 control littermates at 6-8 weeks of age. Rap1 deficient mouse embryonic fibroblasts (MEF) were isolated from 13.5 day embryos, immortalized with SV40LgT, and stably infected with vector, Rap1-wildtype, or Rap1 carrying an isoleucine to arginine mutation at amino acid 312. Total RNA was extracted from MEFs following a similar protocol. The samples were labeled, hybridized, and scanned using standard protocols by the Core Facility at NYU Langone Medical Center on Affymetrix GeneChip Mouse Genome 430 2.0 Arrays.

2013-06-01 | E-GEOD-46209 | biostudies-arrayexpress

Subtelomeric p53 Binding Prevents Accumulation of DNA Damage at Human Telomeres

Project description:Telomeres and tumor suppressor protein TP53 (p53) function in genome protection, but a direct role of p53 at telomeres has not yet been described. Here, we have identified non-canonical p53 binding sites within the human subtelomeres that suppress the accumulation of DNA damage at telomeric repeat DNA. These non-canonical subtelomeric p53 binding sites conferred transcription enhancer-like functions that include an increase in local histone H3K9 and H3K27 acetylation and stimulation of subtelomeric transcripts, including telomere-repeat containing RNA (TERRA). p53 suppressed formation of telomere-associated Î³H2AX and prevented telomere DNA degradation in response to DNA damage stress. Our findings indicate that p53 provides a direct chromatin-associated protection to human telomeres, as well as other fragile genomic sites. We propose that p53-associated chromatin modifications enhance local DNA repair or protection to provide a previously unrecognized tumor suppressor function of p53. p53 binding was analyzed by ChIP-Seq in HCT116 cells treated with camptothecin or untreated control.

2016-01-07 | E-GEOD-75528 | biostudies-arrayexpress

Telomere-Dependent and Telomere-Independent Roles of RAP1 in Regulating Human Stem Cell Homeostasis

Project description:RAP1 is well known as a telomere-binding protein; yet its functions in human stem cells remain unclear. Here we generated RAP1-deficient human embryonic stem cells (hESCs) by CRISPR/Cas9 and obtained RAP1-deficient human mesenchymal stem cells (hMSCs) and neural stem cells (hNSCs) via directed differentiation. In both hMSCs and hNSCs, RAP1 negatively regulated telomere length. In addition, RAP1 acted as a transcriptional regulator of RLEN by tuning the methylation status of its promoter region. Phenotypically, RAP1 deficiency resulted in enhanced self-renewal and delayed senescence in hMSCs rather than in hNSCs, suggesting a complex role of RAP1 in regulating lineage specific stem cell homeostasis. Altogether, these results indicate that RAP1 plays both telomeric and non-telomeric roles in regulating the homeostasis of human stem cells.

2018-11-20 | GSE122654 | GEO

The human TTAGGG Repeat Factors 1 and 2 bind to a subset of interstitial telomeric sequences and satellite repeats

Project description:The study of the proteins that bind to telomeric DNA in mammals has provided a deep understanding of the mechanisms of chromosome-end protection. However, very little is known on the binding of these proteins to nontelomeric DNA sequences. The TTAGGG DNA repeat proteins 1 and 2 (TRF1 and TRF2) bind to mammalian telomeres as part of the shelterin complex and are essential for maintaining chromosome end stability. In this study, we combined chromatin immunoprecipitation with high-throughput sequencing to map at high sensitivity and resolution, the human chromosomal sites to which TRF1 and TRF2 bind. While most of the identified sequences correspond to telomeric regions, we showed that these two proteins also bind to extratelomeric sites. The vast majority of these extra-telomeric sites contains interstitial telomeric sequences (or ITSs). However we also identified non-ITS sites, which are also satellite DNA but the ones mainly constitutive of centromeric and pericentromeric regions. Interestingly, the TRF-binding sites are often located in the proximity of genes or within introns. We propose that, by binding to extratelomeric sequences, TRF1 and TRF2 couple the functional state of telomeres to the long-range organization of chromosomes and gene regulation networks. ChIP-SEQ experiment of transformed human fibroblast BJ cells with 3 antibodies (1 monoclonal anti-TRF1, 1 monoclonal anti-TRF2, 1 polyclonal anti-TRF2) and a negative control (proteinG without antibody used as the ChIP background)

2011-05-03 | E-GEOD-26005 | biostudies-arrayexpress

Expression of subtelomeric lncRNAs links telomeres maintenance with RNA decay in S. cerevisiae

Project description:Long non-coding RNAs (lncRNAs) have been shown to regulate gene expression, chromatin domains and chromosome stability in eukaryotic cells. Recent observations have reported the existence of telomere associated long ncRNAs (TERRA, telomeric repeat containing RNA) in mammalian and yeast cells but their function(s) remain(s) poorly characterized. Here, we report the existence in S. cerevisiae of several sense and antisense Cryptic Unstable Transcripts (CUTs) and Xrn1-sensitive Unstable Transcripts (XUT) initiating within the subtelomeric repeated region Y’. We show that the Y’ ncRNAs, subTERRA, are distinct from TERRA and are mainly destabilized by the general cytoplasmic and nuclear 5’- and 3’- RNA decays in a sense-dependent manner. subTERRA transcription is mainly sustained by RNAPII and subTERRA accumulate preferentially during the G1/S transition and in C-terminal rap1 mutants independently of Rap1p function in silencing. The accumulation of subTERRA in RNA decay mutants coincides with telomere misregulation: shortening of telomere length, loss of telomeric clustering in mitotic cells, indicating that subTERRA might compete with factors involved in telomere elongation, tethering and/or clustering. We propose that subtelomeric RNAs expression links telomere maintenance with RNA degradation pathways. Exmination of two yeast mutants for RNA decay.

2015-04-30 | E-GEOD-67585 | biostudies-arrayexpress

Genome-wide analysis reveals that budding yeast Rif1 binds to replication origins and at blocked replication forks to protect nascent DNA

Project description:This experiment details ChIP sequencing to decipher the binding sites of the Rif1 protein in budding yeast. Rif1 binds most strongly to telomeres where its binding is mediated by Rap1. To reduce telomere binding and help reveal Rap1-independent binding sites, a truncation mutant of Rif1 lacking the Rap1 interaction domain was constructed and analysed. Binding was examined at various cell-cycle stages to elucidate the role of Rif1 in DNA replication and other chromosome transactions.

2018-12-31 | E-MTAB-6736 | biostudies-arrayexpress

Distinct differences in chromatin structure at telomeric X- and Y-elements in budding yeast.

Project description:The telomeric repeat sequences (TGTGG) are the same at all chromosome ends, but the number and position of subtelomeric X and Y repeat elements vary. Using chromatin immunoprecipitation and genome-wide analyses, we here demonstrate that the subtelomeric X and Y elements have distinct structural and functional properties. Y elements are transcriptionally active and highly enriched in histones, whereas X elements are repressed and completely devoid of nucleosomes. In contrast to X elements, the Y elements lack the classical hallmarks of heterochromatin, e.g. high Sir3 and Rap1 occupancy as well as low levels of histone 4 lysine 16 acetylation, Our analyses refute the idea that subtelomeric silencing is a general phenomenon and suggest that the presence of X and Y elements govern the chromatin structure and transcription activtiy at individual chromosome ends. Keywords: nucleosome position and Histone 4 lys 16 acetylation Chip on CHIP

2009-07-01 | GSE13615 | GEO

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