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Subtelomeric CTCF and Cohesin binding site organization using improved subtelomere assemblies and a novel annotation pipeline

ABSTRACT: We investigated the reported binding of telomere associated factor TERF1 and TERF2 to internal telomere sites using ChIP-Seq for these two factors in a lymphoblastoid cell line. We mapped over 40 million reads for each sample to a custom reference genome that incorporates our subtelomere assembly, and generated signal tracks using only uniquely mapping reads, and also using a multimapping pipeline we developed. We find that peaks are misshapen and made up of reads that cannot be distinguished from true telomere sequence. Removing telomere identified reads removes all internal signal.

ORGANISM(S): Homo sapiens

PROVIDER: GSE55053 | GEO | 2014/02/18

SECONDARY ACCESSION(S): PRJNA238475

REPOSITORIES: GEO

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Subtelomeric CTCF and Cohesin binding site organization using improved subtelomere assemblies and a novel annotation pipeline

Project description:We investigated the reported binding of telomere associated factor TERF1 and TERF2 to internal telomere sites using ChIP-Seq for these two factors in a lymphoblastoid cell line. We mapped over 40 million reads for each sample to a custom reference genome that incorporates our subtelomere assembly, and generated signal tracks using only uniquely mapping reads, and also using a multimapping pipeline we developed. We find that peaks are misshapen and made up of reads that cannot be distinguished from true telomere sequence. Removing telomere identified reads removes all internal signal. Examination of TRF1 and TRF2

2014-02-18 | E-GEOD-55053 | biostudies-arrayexpress

Subtelomeric CTCF and cohesin binding site organization using improved subtelomere assemblies and a novel annotation pipeline.

Project description: Not available

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Mapping and initial analysis of human subtelomeric sequence assemblies.

Project description: Not available

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Single cell RNA-seq Analysis of Wild Type(WT), Dcaf11 knockout(KO) and Dcaf11 knockdown(KD) embryos

Project description:Telomeres play vital roles in ensuring chromosome stability and are thus closely linked with the onset of aging and human disease. Telomeres undergo extensive lengthening during early embryogenesis through the so-called alternative lengthening of telomere (ALT) mechanism. However, the detailed molecular mechanism of telomere resetting in early embryos remains unknown. Here, we showed that Dcaf11 participates in telomere elongation in early embryos and 2-cell-like embryonic stem cells (ESCs) in a telomerase-independent manner. The deletion of Dcaf11 in embryos and ESCs leads to reduced telomere sister-chromatid exchange (T-SCE) and impairs telomere lengthening. Importantly, Dcaf11-deficient mice exhibit gradual telomere erosion with successive generations, and hematopoietic stem cell (HSC) activity is greatly compromised. Mechanistically, DCAF11 reactivates Zscan4 and facilitates the removal of heterochromatic H3K9me3 at telomere/subtelomere regions through targeting TRIM28 for ubiquitination-mediated degradation. Our study therefore demonstrates that the ALT factor Dcaf11 plays important roles in telomere elongation in early embryos and ESCs.

2021-01-01 | GSE132745 | 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

Aspergillus fumigatus CEA10 and A1160 reference assemblies

Project description:Telomere to telomere sequence of model Aspergillus fumigatus genomes

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RNA-seq Analysis of Wild Type(WT) and Dcaf11 overexpression (OE) ESCs

Project description:Telomeres play vital roles in ensuring chromosome stability and are thus closely linked with the onset of aging and human disease. Telomeres undergo extensive lengthening during early embryogenesis. However, the detailed molecular mechanism of telomere resetting in early embryos remains unknown. Here, we show that Dcaf11 (Ddb1- and Cul4-associated factor 11) participates in telomere elongation in early embryos and 2-cell-like embryonic stem cells (ESCs). The deletion of Dcaf11 in embryos and ESCs leads to reduced telomere sister-chromatid exchange (T-SCE) and impairs telomere lengthening. Importantly, Dcaf11-deficient mice exhibit gradual telomere erosion with successive generations, and hematopoietic stem cell (HSC) activity is also greatly compromised. Mechanistically, Dcaf11 targets Kap1 (KRAB-associated protein 1) for ubiquitination-mediated degradation, leading to the activation of Zscan4 downstream enhancer and the removal of heterochromatic H3K9me3 at telomere/subtelomere regions. Our study therefore demonstrates that Dcaf11 plays important roles in telomere elongation in early embryos and ESCs through activating Zscan4.

2021-07-17 | GSE180259 | GEO

A technology-agnostic long-read analysis pipeline for transcriptome discovery and quantification

Project description:Alternative splicing is widely acknowledged to be a crucial regulator of gene expression and is a key contributor to both normal developmental processes and disease states. While cost-effective and accurate for quantification, short-read RNA-seq lacks the ability to resolve full-length transcript isoforms despite increasingly sophisticated computational methods. Long-read sequencing platforms such as Pacific Biosciences (PacBio) and Oxford Nanopore (ONT) bypass the transcript reconstruction challenges of short-reads. Here we describe TALON, the ENCODE4 pipeline for analyzing PacBio cDNA and ONT direct-RNA transcriptomes. We apply TALON to three human ENCODE Tier 1 cell lines and show that while both technologies perform well at full-transcript discovery and quantification, each technology has its distinct artifacts. We further apply TALON to mouse cortical and hippocampal transcriptomes and find that a substantial proportion of neuronal genes have more reads associated with novel isoforms than annotated ones. The TALON pipeline for technology-agnostic, long-read transcriptome discovery and quantification tracks both known and novel transcript models as well as expression levels across datasets for both simple studies and larger projects such as ENCODE that seek to decode transcriptional regulation in the human and mouse genomes to predict more accurate expression levels of genes and transcripts than possible with short-reads alone.

2019-06-15 | GSE132766 | GEO

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

Chromatin modifiers and recombination factors promote a telomere fold-back structure, that is lost during replicative senescence

Project description:Telomeres have the ability to adopt a lariat conformation and hence, engage in long and short distance intra-chromosome interactions. Budding yeast telomeres were proposed to fold back into subtelomeric regions, but a robust assay to quantitatively characterize this structure has been lacking. Therefore, it is not well understood how the interactions between telomeres and non-telomeric regions are established and regulated. We employ a telomere chromosome conformation capture (Telo-3C)approach to directly analyze telomere folding and its maintenance in S. cerevisiae. We identify the histone modifiers Sir2, Sin3 and Set2 as critical regulators for telomere folding, which suggests that a distinct telomeric chromatin environment is a major requirement for the folding of yeast telomeres. We demonstrate that telomeres are not folded when cells enter replicative senescence, which occurs independently of short telomere length. Indeed, Sir2, Sin3 and Set2 protein levels are decreased during senescence and their absence may thereby prevent telomere folding. Additionally, we show that the homologous recombination machinery, including the Rad51 and Rad52 proteins, as well as the checkpoint component Rad53 are essential for establishing the telomere fold-back structure. This study outlines a method to interrogate telomere-subtelomere interactions at a single unmodified yeast telomere. Using this method, we provide insights into how the spatial arrangement of the chromosome end structure is established and demonstrate that telomere folding is compromised throughout replicative senescence.

2020-11-20 | PXD021085 | Pride

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