DNA methyation of intragenic CpG islands are required for differentiation from iPSC to NPC
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE156723 | GEO | 2021/01/06
REPOSITORIES: GEO
Similar Datasets
Project description:We wanted to emphisize the role of intragenic CpG island in various cell differentiation. We especially examined the effect of DNA methyltransferase (DNMT) in the neural differentiation from mouse ES cell. Therefore, we performed the Whole-Genome Bisulfite Sequencing (WGBS) analysis of mouse ES cell, ESC-derived NPC, and also in DNMT double knockout (DKO) conditions. By utilizing these result, we confirmed the genes regulated by intragenic CpG island methylation have effect in NPC differentation.
2017-12-30 | GSE82125 | 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
Project description:Human and mouse genomes contain a similar number of CpG islands (CGIs), which are discrete CpG-rich DNA sequences associated with transcription start sites. In both species, about 50% of all CGIs are remote from annotated promoters, but nevertheless often have promoter-like features. To document the role of CGI methylation in cell differentiation, we analysed DNA methylation at a comprehensive CGI set in cells of the mouse hematopoietic lineage. Using a method that potentially detects ~33% of genomic CpGs in the methylated state (>7 million) we found that large differences in gene expression were accompanied by surprisingly few DNA methylation changes. There were, however, many DNA methylation differences between hematopoietic cells and a distantly related tissue, brain. Altered DNA methylation occurred predominantly at CGIs within gene bodies, which have the properties of cell type-restricted promoters, but infrequently at annotated gene promoters or CGI flanking sequences. Elevated intragenic CGI methylation correlated with silencing of the associated gene. Differentially methylated intragenic CGIs tended to lack H3K4me3 and associate with a transcriptionally repressive environment regardless of methylation state. Our results indicate that DNA methylation changes play a relatively minor role in the late stages of differentiation, but point to a distinct role for intragenic CGIs.
2011-05-23 | GSE25578 | GEO
Project description:DNA methyation of intragenic CpG islands are required for differentiation from iPSC to NPC
| PRJNA658906 | ENA
Project description:Human and mouse genomes contain a similar number of CpG islands (CGIs), which are discrete CpG-rich DNA sequences associated with transcription start sites. In both species, about 50% of all CGIs are remote from annotated promoters, but nevertheless often have promoter-like features. To document the role of CGI methylation in cell differentiation, we analysed DNA methylation at a comprehensive CGI set in cells of the mouse hematopoietic lineage. Using a method that potentially detects ~33% of genomic CpGs in the methylated state (>7 million) we found that large differences in gene expression were accompanied by surprisingly few DNA methylation changes. There were, however, many DNA methylation differences between hematopoietic cells and a distantly related tissue, brain. Altered DNA methylation occurred predominantly at CGIs within gene bodies, which have the properties of cell type-restricted promoters, but infrequently at annotated gene promoters or CGI flanking sequences. Elevated intragenic CGI methylation correlated with silencing of the associated gene. Differentially methylated intragenic CGIs tended to lack H3K4me3 and associate with a transcriptionally repressive environment regardless of methylation state. Our results indicate that DNA methylation changes play a relatively minor role in the late stages of differentiation, but point to a distinct role for intragenic CGIs. Mouse immune cells (dendritic cells, B cells, CD4 T cells, Th1 and Th2 cells) were isolated and DNA methylation and gene expression profiled. Methylation and expression patterns were compared to those in brain. For gene expression analysis three biological replicates were used for each cell type.
2011-05-23 | E-GEOD-25578 | biostudies-arrayexpress
Project description:Human and mouse genomes contain a similar number of CpG islands (CGIs), which are discrete CpG-rich DNA sequences associated with transcription start sites. In both species, about 50% of all CGIs are remote from annotated promoters, but nevertheless often have promoter-like features. To document the role of CGI methylation in cell differentiation, we analysed DNA methylation at a comprehensive CGI set in cells of the mouse hematopoietic lineage. Using a method that potentially detects ~33% of genomic CpGs in the methylated state (>7 million) we found that large differences in gene expression were accompanied by surprisingly few DNA methylation changes. There were, however, many DNA methylation differences between hematopoietic cells and a distantly related tissue, brain. Altered DNA methylation occurred predominantly at CGIs within gene bodies, which have the properties of cell type-restricted promoters, but infrequently at annotated gene promoters or CGI flanking sequences. Elevated intragenic CGI methylation correlated with silencing of the associated gene. Differentially methylated intragenic CGIs tended to lack H3K4me3 and associate with a transcriptionally repressive environment regardless of methylation state. Our results indicate that DNA methylation changes play a relatively minor role in the late stages of differentiation, but point to a distinct role for intragenic CGIs.
2011-05-23 | GSE25688 | GEO
Project description:The lysine acetyltransferase KAT6A (MOZ, MYST3) belongs to the MYST family of chromatin regulators, facilitating histone acetylation. Dysregulation of KAT6A has been implicated in developmental syndromes and the onset of acute myeloid leukemia (AML). Previous work suggests that KAT6A is recruited to its genomic targets by a combinatorial function of histone binding PHD fingers, transcription factors and chromatin binding interaction partners. Here, we demonstrated that a winged helix domain at the N-terminus of KAT6A specifically interacts with unmethylated CpG motifs. This DNA binding function leads to the association of KAT6A to unmethylated CpG islands (CGIs) genome wide. Mutation of the essential amino acids completely abrogates the enrichment of KAT6A at CGIs. Overexpression of a KAT6A WH1 mutant has a dominant negative effect on H3K9 histone acetylation, which is comparable to the effects upon overexpression of a KAT6A HAT domain mutant. Taken together, our work revealed a previously unrecognized chromatin recruitment mechanism of KAT6A, offering a new perspective on the role of KAT6A in gene regulation and human diseases
2023-01-14 | PXD034833 | Pride
Project description:We wanted to emphisize the role of intragenic CpG island in various cell differentiation. We especially examined the effect of DNA methyltransferase (DNMT) in the neural differentiation from mouse ES cell. Therefore, we performed the transcriptome analysis of mouse ES cell, ESC-derived NPC, and also in DNMT double knockout (DKO) conditions. By utilizing these result, we confirmed the genes regulated by intragenic CpG island methylation have effect in NPC differentation.
2017-12-30 | GSE81925 | GEO
Project description:Human and mouse genomes contain a similar number of CpG islands (CGIs), which are discrete CpG-rich DNA sequences associated with transcription start sites. In both species, about 50% of all CGIs are remote from annotated promoters, but nevertheless often have promoter-like features. To document the role of CGI methylation in cell differentiation, we analysed DNA methylation at a comprehensive CGI set in cells of the mouse hematopoietic lineage. Using a method that potentially detects ~33% of genomic CpGs in the methylated state (>7 million) we found that large differences in gene expression were accompanied by surprisingly few DNA methylation changes. There were, however, many DNA methylation differences between hematopoietic cells and a distantly related tissue, brain. Altered DNA methylation occurred predominantly at CGIs within gene bodies, which have the properties of cell type-restricted promoters, but infrequently at annotated gene promoters or CGI flanking sequences. Elevated intragenic CGI methylation correlated with silencing of the associated gene. Differentially methylated intragenic CGIs tended to lack H3K4me3 and associate with a transcriptionally repressive environment regardless of methylation state. Our results indicate that DNA methylation changes play a relatively minor role in the late stages of differentiation, but point to a distinct role for intragenic CGIs. Mouse immune cells (dendritic cells, B cells, CD4 T cells, Th1 and Th2 cells) were isolated and DNA methylation and gene expression profiled. Methylation and expression patterns were compared to those in brain. DNA methylation was profiled using MAP-seq and two replicates were carried out for each cell type of interest.
2011-05-23 | E-GEOD-25688 | biostudies-arrayexpress
Project description:We have systematically profiled DNA methylation at promoter CpG islands (CGIs) in ovarian cancer. Epithelial ovarian tumours, excluding mucinous and clear cell cancers, prospectively collected through a cohort study, were analyzed by differential methylation hybridization (DMH) (Nouzova M et al, 2004) in duplicates. The loci targeted by the custom-designed microarray are the promoter CpG islands (Gardiner-Garden and Frommer, 1987) of the genes involved in the Wnt, p53, AKT/mTOR, BRCA1/2 and Redox pathways, DNA repair (HR, NHEJ and MMR), FA family and IgLON family.
2011-06-01 | GSE23240 | GEO