RNA Seq to identify novel transcripts originating from orphan CGIs
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE123951 | GEO | 2019/06/27
REPOSITORIES: GEO
Similar Datasets
Project description:RNA Seq to identify novel transcripts originating from orphan CGIs
| PRJNA510378 | ENA
Project description:The human genome contains approximately 27,700 CpG islands (CGIs). Most are associated with promoters and their DNA is nearly always unmethylated. By contrast, CGIs lying within the bodies of genes usually become methylated during differentiation and development. CGIs also normally become methylated at X-inactivated and imprinted genes and abnormally methylated in genome rearrangements and in malignancy. In such circumstances, methylation of CGIs is often associated with RNA transcripts reading through these elements but the relationship of this RNA to methylation of CGIs is not clear. Here we investigated a previously described form of α-thalassemia caused by a genome rearrangement leading to abnormal transcription and DNA methylation of the CGI at the promoter of the α-globin gene. We show that transcription per se is responsible for DNMT3B-mediated methylation of the globin CGI, and that this is a general mechanism responsible for methylation of most intragenic CpG islands.
2017-08-10 | GSE84353 | GEO
Project description:The human genome contains approximately 27,700 CpG islands (CGIs). Most are associated with promoters and their DNA is nearly always unmethylated. By contrast, CGIs lying within the bodies of genes usually become methylated during differentiation and development. CGIs also normally become methylated at X-inactivated and imprinted genes and abnormally methylated in genome rearrangements and in malignancy. In such circumstances, methylation of CGIs is often associated with RNA transcripts reading through these elements but the relationship of this RNA to methylation of CGIs is not clear. Here we investigated a previously described form of α-thalassemia caused by a genome rearrangement leading to abnormal transcription and DNA methylation of the CGI at the promoter of the α-globin gene. We show that transcription per se is responsible for DNMT3B-mediated methylation of the globin CGI, and that this is a general mechanism responsible for methylation of most intragenic CpG islands.
2017-08-10 | GSE84352 | GEO
Project description:The human genome contains approximately 27,700 CpG islands (CGIs). Most are associated with promoters and their DNA is nearly always unmethylated. By contrast, CGIs lying within the bodies of genes usually become methylated during differentiation and development. CGIs also normally become methylated at X-inactivated and imprinted genes and abnormally methylated in genome rearrangements and in malignancy. In such circumstances, methylation of CGIs is often associated with RNA transcripts reading through these elements but the relationship of this RNA to methylation of CGIs is not clear. Here we investigated a previously described form of α-thalassemia caused by a genome rearrangement leading to abnormal transcription and DNA methylation of the CGI at the promoter of the α-globin gene. We show that transcription per se is responsible for DNMT3B-mediated methylation of the globin CGI, and that this is a general mechanism responsible for methylation of most intragenic CpG islands.
2017-08-10 | GSE84354 | GEO
Project description:While the majority of RNA polymerase II initiation events in mammalian genomes take place within CpG island (CGI) promoters, our understanding of their regulation remains limited. Here we combine single-molecule footprinting with interaction proteomics to identify BANP as a critical CGI regulator and the long sought-after TF that binds the orphan CGCG element in mouse and human. We show that BANP drives the activity of essential metabolic genes in the mouse genome in pluripotent and terminally differentiated cells. However, BANP binding is strongly repelled by DNA methylation of its motif in vitro and in vivo, which epigenetically restricts most binding to CGIs and accounts for its absence at aberrantly methylated CGIs in cancer cells. Upon binding to an unmethylated motif, BANP opens chromatin and phases nucleosomes. Our results establish Banp as a critical activator and put forth a model whereby CGI promoter activity relies on methylation-sensitive TFs capable of chromatin opening.
2021-06-16 | PXD024794 | Pride
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:Most sarcomas have complex karyotype and are characterized by multiple chromosomal rearrangements. Moreover, sarcomas very frequently maintain their telomeres by recombination in the process called Alternative Lengthening of Telomeres (ALT) which enables their continuous growth and immortalization. Previously our group showed that orphan receptors bind specifically to the ALT telomeres and that their presence is important for the ALT mechanism. In these studies we focus on the function of orphan receptors at the telomeres and their contribution to telomeric recombination. We demonstrate that orphan receptors induce proximity of their binding sites in telomeric and genomic context and reveal novel aspects of ALT which are telomere-genome rearrangements which can underlie complexity of sarcomas. Our data perturb the dogma of telomere function in protecting the genome integrity. Here we show that in some cases telomeres may in fact drive genomic instability and chromosomal rearrangements by recombination with genomic sites. Characterization of TRF2 and orphan receptor NR2F/C2 binding sites in ALT (-) and ALT (+) cells.
2015-02-23 | E-GEOD-46237 | 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: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:Cells contain numerous abundant molecular machines assembled from multiple subunits. Imbalances in subunit production and failed assembly generate orphan subunits that are eliminated by poorly defined pathways. Here, we determined how orphan subunits of the cytosolic chaperonin CCT are recognized. Several unassembled CCT subunits recruited the E3 ubiquitin ligase HERC2 using ZNRD2 as an adaptor. Both factors were necessary for orphan CCT subunit degradation in cells, sufficient for CCT subunit ubiquitination with purified factors, and necessary for optimal cell fitness. Domain mapping and structure prediction defined the molecular features of a minimal HERC2-ZNRD2-CCT module. The structural model, whose key elements were validated in cells using point mutants, shows why ZNRD2 selectively recognizes multiple orphaned CCT subunits without engaging assembled CCT. Our findings reveal how failures during CCT assembly are monitored and provide a paradigm for the molecular recognition of orphan subunits, the largest source of quality control substrates in cells.
2023-07-26 | PXD042773 | Pride