Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

11 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Epigenetic conservation at gene regulatory elements revealed by non-methylated DNA profiling in seven vertebrates

ABSTRACT: Two-thirds of gene promoters in mammals are associated with regions of non-methylated DNA, called CpG islands (CGIs), which counteract the repressive effects of DNA methylation. In lower vertebrates, computational CGI predictions often reside away from gene promoters, suggesting a major divergence in gene promoter architecture across vertebrates. By experimentally identifying non-methylated DNA in the genomes of seven diverse vertebrates, we instead reveal that non-methylated islands (NMIs) of DNA are a central feature of vertebrate gene promoters. Furthermore, NMIs are present at orthologous genes across vast evolutionary distances, revealing a surprising level of conservation in this epigenetic feature. By profiling NMIs in different tissues and developmental stages we uncover a unifying set of features that are central to the function of NMIs in vertebrates. Together these findings demonstrate an ancient logic for NMI usage at gene promoters and reveal an unprecedented level of epigenetic conservation across vertebrate evolution. Bio-CAP was used to identify non-methylated regions of the genome in seven diverse vertebrates (human, mouse, platypus, chicken, lizard, frog and zebrafish) across a number of tissues.

ORGANISM(S): Xenopus (Silurana) tropicalis

SUBMITTER: David Sims

PROVIDER: E-GEOD-43512 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

BioCAP-Seq analysis of human chromosome 21 after its passage through either the mouse male germline

Project description:This study aims to investigate whether the passage of human chromosome 21 through the mouse male germline results in changes in the transcriptional deployment of the exogenous chromosome in the offspring generation. We used the Tc1 mouse model that stably carries almost an entire copy of human chromosome 21 and profiled the genome-wide pattern of non-methylated DNA using BioCAP-sequencing (doi: 10.1093/nar/gkr1207) in the livers of male- and female-germline derived Tc1 mice. This dataset contains only the samples for male-germline derived animals, BioCAP-Seq data for female-germline derived animals have already been deposited in Gene Expression Omnibus with the accession number GSE72208.

2016-11-16 | E-MTAB-4930 | biostudies-arrayexpress

Functional characterisation of CpG islands in human and mouse tissues

Project description:Tissue-specific methylation patterns suggest a role for CpG island (CGI) methylation in differentiation and cell-type-specific gene regulation. We have applied CXXC affinity purification (CAP), MBD affinity purification (MAP) and chromatin immunoprecipitation (ChIP) in combination with solexa sequencing to investigate the extent and functional significance of CGI methylation in sperm, blood, cerebellum and ES cells for both human and mouse.

2014-01-21 | E-ERAD-11 | biostudies-arrayexpress

The role of CpG island methylation in immune cell gene regulation

Project description:Tissue-specific methylation patterns suggest a role for CpG island methylation in differentiation and cell-type-specific gene regulation. We have profiled CpG island methylation in different cells of the immune cell lineage to investigate this role. MBD-affinity purification combined with next generation sequencing was used to analyse CpG island methylation in dendritic cells, B cells, Th1, Th2 and naïve T cells. ChIP-seq was carried out to determine RNA polymerase II binding sites in these cell types and this was compared to the methylation profiles obtained. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/ Abstract: We have profiled CpG island methylation in various immune system cell types and related this to gene expression in these cells.

2011-11-10 | E-ERAD-27 | biostudies-arrayexpress

Deletion of KDM2B DNA-binding domain affects RING1B and SUZ12 occupancy

Project description:The histone lysine demethylase protein, KDM2B, associates with the PCGF1/PRC1 complex and binds to non-methylated DNA through its ZF-CxxC domain, providing a possible molecular link between CpG island elements and polycomb nucleation (Farcas et al., 2012, Wu et al., 2013). Here, a novel genetic system was designed in which PCGF1/PRC1 targeting could be disrupted in vivo through the ablation of KDM2B-mediated DNA binding. To ablate PCGF1/PRC1 targeting, an exon that encodes most of the KDM2B ZF-CxxC domain and is shared by both the long and short form of the protein was flanked by loxP sites (Kdm2bfl/fl). Homozygous mouse ES cell lines were derived that also stably express a tamoxifen inducible form of CRE-recombinase. CRE induced deletion of the ZF-CxxC domain by the addition of tamoxifen yields KDM2B long and short form proteins that are incapable of binding to CpG island DNA but still remain associated with the PCGF1/PRC1 variant complex. We then assessed genome-wide occupancy of the PRC1 component RING1B and the PRC2 component SUZ12 to examine the impact of losing KDM2B-dependent targeting of polycomb. KDM2Bfl/fl ES cells were treated with 800M-BM-5M tamoxifen for 72hours and compared to untreated control cells by ChIP-seq for KDM2B, RING1B and SUZ12, and RNA-seq.

2014-05-27 | E-GEOD-52619 | biostudies-arrayexpress

Coordination of engineered factors with TET1/2 promotes early stage epigenetic modification during somatic cell reprogramming

Project description:Somatic cell reprogramming towards induced pluripotent stem cells (iPSCs) holds great promise in future regenerative medicine, however, the reprogramming process mediated by the traditional defined factors (OSNK) is slow and extremely inefficient. Here we show that a combination of modified reprogramming factors (OySyNyK), in which the transactivation domain of the Yes-associated protein is fused to OCT4, SOX2 and NANOG respectively, could be used to establish a highly efficient and rapid reprogramming system for iPSC generation. We show that the efficiency of OySyNyK-induced iPSCs was up to 100-fold higher than that of induction by traditional OSNK. Moreover we show that the reprogramming by OySyNyK is very rapid (initiated at 24 h versus 5 d by OSNK). Compared with OSNK, we found that OySyNyK factors significantly increased the expression of Tet1/2 at the early stage, which will interact with OSNK factors, and co-occupy pluripotency loci in the genome for somatic cell reprogramming. Our studies not only establish a rapid and highly efficient iPSC reprogramming system, but also uncover a novel mechanism by which OSNK factors coordinate with TET proteins to regulate 5hmC-mediated epigenetic control, thereby promoting somatic cell reprogramming. We examined DNA hydroxymethylation progression of reprogramming intermediates. To this end, we profiled the genome-wide 5hmC distribution in MEFs, the reprogramming intermediates at different stages induced by either the OSNK or OySyNyK methods, and iPSCs using the chemical capture approach

2013-08-08 | E-GEOD-46202 | biostudies-arrayexpress

Identification of a novel set of DNA methylation markers in bladder cancer using MBD-methylCap/seq and urine DNA screening in a Chinese population

Project description:The aim of the present study was to identify novel DNA methylation markers in bladder cancer (BCa) through genome-wide profiling of bladder cancer cell lines and subsequent MSP screening in urine samples. Experimental Design: MBD methylCap/seq was carried out to screen differentially methylated CpG islands using two BCa cell lines (5637 and T24) and two normal bladder mucosa (BM) samples. The top one hundred most hypermethylated targets were screened using Methylation Specific PCR (MSP) in small and big cohort of urine samples from BCa patients and normal controls. The diagnostic performance of the gene panel was further evaluated in different clinical scenarios. Results: In total, 1,627 gene promoter regions hypermethylated in BCa cell line were identified in genomic level methylation profiling. The followed screening procedure in clinical urine sample generated eight genes (VAX1, KCNV1, ECEL1, TMEM26, TAL1, PROX1, SLC6A20, and LMX1A) capable of differentiating BCa from normal control. Subsequent validation in a large sample size enabled the optimisation of 5 methylation targets (VAX1, KCNV1, TAL1, PPOX1 and CFTR) for BCa diagnosis with sensitivity and specificity of 86.32% and 87.13%, respectively. In addition, VAX1 and LMX1A methylation could predict the tumour recurrence. Conclusions: Tumor specific biomarkers of BCa could be established by first performing genome level methylation profiling with cell lines and then screening the potential targets in urine samples. The panel of methylated genes identified was promising for the early non-invasive detection and surveillance of BCa. MBD methylCap/seq was carried out to screen differentially methylated CpG islands using two BCa cell lines (5637 and T24), and two normal bladder tissue mix as control.

2012-04-30 | E-GEOD-33839 | biostudies-arrayexpress

A SNF2 protein targets variable copy number repeats and thereby influences allele-specific expression

Project description:ATRX is an X-linked gene of the SWI/SNF family whose role in vivo is currently unknown. Mutations in ATRX cause syndromal mental retardation. ATRX binds to tandem repeat (TR) sequences both in heterochromatin (e.g. telomeres) and euchromatin. Genes associated with these TRs can be dysregulated when ATRX is mutated and the degree to which their expression changes is determined by the size of the TR, producing skewed allelic expression. This explains the nature of the affected genes, the variable phenotypes seen with identical ATRX mutations and also illustrates a new mechanism underlying variable penetrance. Many of the TRs in ATRX targets are G-rich and predicted to form non-B DNA structures (including G quadruplex) in vivo. We have shown that ATRX binds G quadruplex structures in vitro suggesting a mechanism by which ATRX may play a role in various nuclear processes and how this is perturbed when ATRX is mutated. 4 Human Erythroblast, 1 HEP3B and 1 Fibroblast ChIP-ChIP Sample For ChIP-Seq: one human erythroblasts, one mouse ES, one human erythroblast reference Sample, and one mouse ES input reference Sample.

2010-11-02 | E-GEOD-22162 | biostudies-arrayexpress

Active DNA demethylation during the vertebrate phylotypic period

Project description:The vertebrate body plan and organs are shaped during a highly conserved embryonic phase called the phylotypic stage, however the mechanisms that guide the epigenome through this transition and their evolutionary conservation remain elusive. Here we report widespread DNA demethylation of thousands of enhancers during the phylotypic period in zebrafish, Xenopus and mouse. These dynamic enhancers are linked to essential developmental genes that display coordinated transcriptional and epigenomic changes in the diverse vertebrates during embryogenesis. Phylotypic stage-specific binding of Tet proteins to (hydroxy)methylated DNA, and enrichment of hydroxymethylcytosine on these enhancers, implicated active DNA demethylation in this process. Furthermore, loss of function of Tet1/2/3 in zebrafish caused reduced chromatin accessibility and increased methylation levels specifically on these enhancers, indicative of DNA methylation being an upstream regulator of phylotypic enhancer function. Overall, our study reveals a novel regulatory module associated with the most conserved phase of vertebrate embryogenesis and uncovers an ancient developmental role for the Tet dioxygenases.

2016-01-27 | PXD001164 | Pride

Sigma38 binding sites in E. Coli

Project description:ChIP-seq to identify sigma38 binding sites in wild-type and delta ssrS (6S RNA knockout) strains of E. Coli K-12 MG1655, during stationary phase ChIP-seq using antibody against sigma38 in wild-type and ssrS deletion strain. Two replicates for wild type and one replicate for ssrS deletion.

2016-06-10 | E-GEOD-74836 | biostudies-arrayexpress

A Primary Role of TET Proteins in Establishment and Maintenance of De Novo Bivalency at CpG Islands of Developmental Genes

Project description:TET protein-catalyzed 5mC oxidation not only creates novel DNA modifications such as 5hmC, but also initiates active or passive DNA demethylation. However, the TETsâ function in crosstalk with specific histone modifications is largely elusive. Here, we show that TET2-mediated DNA demethylation plays a primary role in the de novo establishment and maintenance of H3K4me3/H3K27me3 bivalent domain underlying the methylated DNA CpG islands (CGIs). Overexpression of wild type (WT) but not catalytic inactive mutant (Mut) TET2 in TET-low-expressing cells results in increase of 5hmC level and accompanying DNA demethylation at a subset of CGIs. Importantly, this is sufficient to create de novo bivalent domains at these loci. Genome-wide analysis reveals that these de novo synthesized bivalent domains are largely associated with a subset of key developmental gene promoters, which are often located within CpG islands that are previously hyper-methylated and silenced. On the other hand, depletion of Tet1 and Tet2 in mouse ES cells results in an apparent loss of H3K27me3 at bivalent domains, which are located within CGIs and associated with a particular set of key developmental gene promoters. Collectively, these data suggest that TET proteins have a primary role in charge of regulating the crosstalk between two key epigenetic mechanisms, DNA methylation and histone methylation (H3K4me3 and H3K27me3), particularly at a subset of CpG islands associated with developmental genes. We examined H3K4me3,H3K27me3,5mC and 5hmC in 293T and mES cell types,using Illumina Hiseq2500.

2016-07-25 | E-GEOD-72481 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data