Comprehensive analysis of orphan CpG islands identifes novel promoters with conserved DNA methylation dynamics
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA126345 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR040498.fastq.gz | Fastqsanger.gz | |||
| SRR040499.fastq.gz | Fastqsanger.gz | |||
| SRR040500.fastq.gz | Fastqsanger.gz | |||
| SRR040501.fastq.gz | Fastqsanger.gz | |||
| SRR040502.fastq.gz | Fastqsanger.gz |
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Project description:We report the application of single molecule-based sequencing technology in combination with CXXC affinity purifcation (CAP-seq), MBD affinity purification (MAP-seq) and chromatin immunoprecipitation (ChIP-seq) to generate reciprocal methylation and chromatin modifcation maps in human and mouse. We find that contrary to sequence based prediction methods that humans and mice possess highly equivalent compliments of CpG islands (CGIs). The majority of these CGIs are positive for the active histone modification; H3K4me3 in embryonic stem cells (ES cells) the magnitude of which is correlated with the local density of non-methylated CpG. Approximately half of the human and mouse CGIs are distal to annotated gene promoters, yet more than 40% identify unanticipated transcription start sites as defined by RNA polymerase occupancy and published RNA mapping data. These orphans CGIs preferentially acquire DNA methylation in somatic cells, and this corresponds with a loss of H3K4me3 and RNA polymerase II at these sites. Conversely abnormal CGI methylation found in colorectal tumours showed a distinct distribution relative to that found in normal somatic tissues displaying preferential association with loci marked by H3K27me3 in human ES cells. This study provides a comprehensive functional assessment of CGIs in normal and diseased tissues. Examination of CGI methylation status in human and mouse primary tissues.
2010-10-04 | E-GEOD-21442 | biostudies-arrayexpress
Project description:We report the application of single molecule-based sequencing technology in combination with CXXC affinity purifcation (CAP-seq), MBD affinity purification (MAP-seq) and chromatin immunoprecipitation (ChIP-seq) to generate reciprocal methylation and chromatin modifcation maps in human and mouse. We find that contrary to sequence based prediction methods that humans and mice possess highly equivalent compliments of CpG islands (CGIs). The majority of these CGIs are positive for the active histone modification; H3K4me3 in embryonic stem cells (ES cells) the magnitude of which is correlated with the local density of non-methylated CpG. Approximately half of the human and mouse CGIs are distal to annotated gene promoters, yet more than 40% identify unanticipated transcription start sites as defined by RNA polymerase occupancy and published RNA mapping data. These orphans CGIs preferentially acquire DNA methylation in somatic cells, and this corresponds with a loss of H3K4me3 and RNA polymerase II at these sites. Conversely abnormal CGI methylation found in colorectal tumours showed a distinct distribution relative to that found in normal somatic tissues displaying preferential association with loci marked by H3K27me3 in human ES cells. This study provides a comprehensive functional assessment of CGIs in normal and diseased tissues.
2010-10-05 | GSE21442 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE38560: CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters (RNA-seq) GSE38561: CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters (ChIP-seq) GSE38562: CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters (genomic SEQ) GSE38563: CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters (MNase-seq) GSE38564: CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters (5) Refer to individual Series
2012-06-11 | E-GEOD-38577 | biostudies-arrayexpress
Project description:To gain insights into the function of DNA methylation and its impact on gene expression, we measured methylation in 19,530 mouse promoters and CpG islands. Keywords: DNA methylation, MeDIP The chosen array from NIMBLEGEN (2007-02-27_MM8_ CpG island _ promoter array) represents putative mouse promoters plus CpG islands, each covered by oligonucleotide probes spanning 1.3 kb upstream and 0.5 kb downstream of the transcription start site.
2009-07-30 | E-GEOD-12301 | biostudies-arrayexpress
Project description:CpG islands (CGIs) are vertebrate genomic landmarks that encompass the promoters of most genes and often lack DNA methylation. Querying their apparent importance, the number of CGIs is reported to vary widely in different species and many do not co-localise with annotated promoters. We set out to quantify the number of CGIs in mouse and human genomes using CXXC Affinity Purification plus deep sequencing (CAP-seq). We also asked whether CGIs not associated with annotated transcripts share properties with those at known promoters. We found that, contrary to previous estimates, CGI abundance in humans and mice is very similar and many are at conserved locations relative to genes. In each species CpG density correlates positively with the degree of H3K4 trimethylation, supporting the hypothesis that these two properties are mechanistically interdependent. Approximately half of mammalian CGIs (>10,000) are "orphans" that are not associated with annotated promoters. Many orphan CGIs show evidence of transcriptional initiation and dynamic expression during development. Unlike CGIs at known promoters, orphan CGIs are frequently subject to DNA methylation during development, and this is accompanied by loss of their active promoter features. In colorectal tumors, however, orphan CGIs are not preferentially methylated, suggesting that cancer does not recapitulate a developmental program. Human and mouse genomes have similar numbers of CGIs, over half of which are remote from known promoters. Orphan CGIs nevertheless have the characteristics of functional promoters, though they are much more likely than promoter CGIs to become methylated during development and hence lose these properties. The data indicate that orphan CGIs correspond to previously undetected promoters whose transcriptional activity may play a functional role during development.
| S-EPMC2944787 | biostudies-literature
Project description:To gain insights into the function of DNA methylation and its impact on gene expression, we measured methylation in 19,530 mouse promoters and CpG islands. Keywords: DNA methylation, MeDIP
2009-07-30 | GSE12301 | GEO
Project description:CpG islands (CGIs) represent a unique and widespread genetic feature of vertebrate genomes, being associated with ~70% of all annotated gene promoters. CGIs have been proposed to control transcription initiation by conferring nearby promoters with unique chromatin properties. In addition, there are thousands of distal or orphan CGIs (oCGIs) whose functional relevance and mechanism of action are barely known. Here we show that oCGIs are an essential component of poised enhancers (PEs) that boost their long-range regulatory activity and dictate the responsiveness of their target genes. Using a CRISPR/Cas9 knock-in strategy in mESC, we introduced PEs with or without oCGIs within topological associating domains (TADs) harbouring genes with different types of promoters. By evaluating the chromatin, topological and regulatory properties of the engineered PEs, we uncovered that, rather than increasing their local activation, the oCGI boost the physical and functional communication between PEs and distally located developmental genes. Furthermore, we demonstrate that developmental genes with CpG rich promoters are particularly responsive to PEs and that such responsiveness depends on the presence of oCGI. Therefore, our work unveils a novel role for CGIs as genetic determinants of the compatibility between genes and enhancers, which has major implications for the current understanding of how developmental gene expression programs are deployed as well as for our ability to predict the pathological consequences of human structural variation.
2020-08-20 | GSE156465 | GEO
Project description:CpG island elements are associated with most mammalian gene promoters, yet how they contribute to gene regulation remains poorly understood. Recently it has become clear that a subset of CpG islands in embryonic stem cells can act as polycomb response elements and are recognized by the polycomb silencing systems to regulate the expression of genes involved in pluripotency and early developmental transcription programs. How CpG islands function mechanistically as nucleation sites for polycomb repressive complexes remains unknown. Here we discover that the KDM2B protein, by virtue of its ZF-CxxC DNA binding domain, specifically recognizes non-methylated DNA in CpG islands elements genome-wide. Through a physical interaction with the polycomb repressive complex 1 (PRC1), KDM2B targets PRC1 to CpG islands where it contributes to H2AK119ub1 and gene repression at a subset of polycomb targets. Unexpectedly, we also find that CpG islands are occupied by low levels of PRC1 throughout the genome, suggesting that the KDM2B-PRC1 complex may sample CpG island associated genes for susceptibility to polycomb mediated silencing. These observations demonstrate an unexpected and direct link between recognition of CpG islands by KDM2B and targeting of the polycomb repressive system. This provides the basis for a new model describing the functionality of CpG islands as mammalian PREs.
2012-12-26 | GSE40860 | GEO
Project description:Transcription factors that bind small DNA motifs embedded in promoters play a central role in controlling gene expression. However, in addition to these elements, up to 70% of genes in higher eukaryotes also have high levels of non-methylated cytosine/guanine base pairs (CpGs) surrounding promoters and gene regulatory units. These features, called CpG islands, were identified over twenty years ago but there remains little mechanistic evidence to suggest how these enigmatic elements contribute to promoter function, with the exception that they are refractory to epigenetic silencing by DNA methylation. Here we show that CpG islands directly recruit the H3K36 specific lysine demethylase enzyme KDM2A. Genome wide analyses by ChIP-seq demonstrated a striking global association of KDM2A with CpG islands. Nucleation of KDM2A at these elements resulted in removal of H3K36 methylation creating CpG island chromatin that is uniquely depleted of this modification. KDM2A utilizes a zinc finger CxxC (ZF-CxxC) domain that specifically recognizes non-methylated CpG DNA and binding is blocked when the CpG DNA is methylated, thus constraining KDM2A to nonmethylated CpG islands. These data expose a remarkably straightforward mechanism through which KDM2A delineates a unique architecture that differentiates CpG island chromatin from bulk chromatin.
2010-04-27 | GSE21201 | GEO
Project description:CpG-islands (CGIs) are key regulatory DNA elements at most promoters, but how they influence the chromatin status and transcription remains elusive. Here we identify and characterize SAMD1 (SAM domain-containing protein 1) as an unmethylated CGI-binding protein. SAMD1 possesses an atypical winged-helix domain that directly recognizes unmethylated CpG-containing DNA via simultaneous interactions with both the major and the minor groove. The SAM domain interacts with L3MBTL3, but it can also homopolymerize into a closed pentameric ring. At a genome-wide level, SAMD1 localizes to H3K4me3-decorated CGIs, where it acts as a repressor. SAMD1 tethers L3MBTL3 to chromatin and interacts with the KDM1A histone demethylase complex to modulate H3K4me2 and H3K4me3 levels at CGIs, thereby providing a mechanism for SAMD1-mediated transcriptional repression. Absence of SAMD1 impairs ES cell differentiation processes, leading to mis-regulation of key biological pathways. Together, our work establishes SAMD1 as a novel chromatin regulator acting at unmethylated CGIs.
2021-05-13 | PXD016781 | Pride