Cell Type-Specific DNA Methylation at Intragenic CpG Islands in the Immune System
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE25689 | GEO | 2011/05/23
SECONDARY ACCESSION(S): PRJNA135839
REPOSITORIES: GEO
Similar Datasets
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, ∼50% of all CGIs are remote from annotated promoters but, nevertheless, often have promoter-like features. To determine the role of CGI methylation in cell differentiation, we analyzed 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, 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 in the immune system 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 (CGI "shores"). Unexpectedly, 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 and suggest that intragenic CGIs represent regulatory sites of differential gene expression during the early stages of lineage specification.
| S-EPMC3129250 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2011-05-23 | E-GEOD-25689 | 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. 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 | GSE25578 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-12-30 | GSE82142 | 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: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 human genome contains ?30,000 CpG islands (CGIs). While CGIs associated with promoters nearly always remain unmethylated, many of the ?9,000 CGIs lying within gene bodies become methylated during development and differentiation. Both promoter and intragenic CGIs may also become abnormally methylated as a result of genome rearrangements and in malignancy. The epigenetic mechanisms by which some CGIs become methylated but others, in the same cell, remain unmethylated in these situations are poorly understood. Analyzing specific loci and using a genome-wide analysis, we show that transcription running across CGIs, associated with specific chromatin modifications, is required for DNA methyltransferase 3B (DNMT3B)-mediated DNA methylation of many naturally occurring intragenic CGIs. Importantly, we also show that a subgroup of intragenic CGIs is not sensitive to this process of transcription-mediated methylation and that this correlates with their individual intrinsic capacity to initiate transcription in vivo. We propose a general model of how transcription could act as a primary determinant of the patterns of CGI methylation in normal development and differentiation, and in human disease.
| S-EPMC5594649 | biostudies-literature
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: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