Integrative analysis of methylome and transcriptome in human blood identifies extensive sex and immune cell-specific differentially methylated regions
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PROVIDER: PRJNA290670 | ENA |
REPOSITORIES: ENA
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Project description:DNA methylation has an impact on regulation of gene expression, however the relation between the two is complex. By performing an integrative analysis of the methylome and transcriptome of the four main circulating immune cell-subsets from healthy females, namely B cells, monocytes, CD4 and CD8 T cells, the relation between the two was characterized. In addition, in light of the known sex bias in the prevalence of several immune-mediated diseases, the female datasets were compared with similar public available male datasets. Immune subset-specific differentially methylated regions (DMRs) were found to be highly similar between males and females; however numerous sex-specific DMRs shared by the four leukocytes subsets were identified, most located on autosomal chromosomes. This provides a list of highly interesting candidate genes to be studied in diseases with sexual dimorphism like autoimmunity. Immune cell-specific DMRs were mainly located in the gene body and intergenic region, distant from CpG islands but overlapping with enhancer elements, thus indicating the importance of distal regulatory elements in leukocyte subsets. In contrast; sex-specific DMRs were over-represented in CpG islands, suggesting some difference in regulation between sex and immune-cell specificity. Both positive and negative correlations between cell-specific expression and methylation were observed, with negative correlation being more frequent. Our acquired immune cell- and sex- specific methylome and transcriptome profiles provide novel insight on their complex regulatory interactions, and may particularly contribute to research of immune-mediated diseases. DNA purified from isolated 5 cell subsets (monocyte, B cells, CD4 T cells, CD8 T cells and PBMCs) obtained from 6 healthy female donors
2016-07-01 | E-GEOD-71244 | biostudies-arrayexpress
Project description:DNA methylation has an impact on regulation of gene expression, however the relation between the two is complex. By performing an integrative analysis of the methylome and transcriptome of the four main circulating immune cell-subsets from healthy females, namely B cells, monocytes, CD4 and CD8 T cells, the relation between the two was characterized. In addition, in light of the known sex bias in the prevalence of several immune-mediated diseases, the female datasets were compared with similar public available male datasets. Immune subset-specific differentially methylated regions (DMRs) were found to be highly similar between males and females; however numerous sex-specific DMRs shared by the four leukocytes subsets were identified, most located on autosomal chromosomes. This provides a list of highly interesting candidate genes to be studied in diseases with sexual dimorphism like autoimmunity. Immune cell-specific DMRs were mainly located in the gene body and intergenic region, distant from CpG islands but overlapping with enhancer elements, thus indicating the importance of distal regulatory elements in leukocyte subsets. In contrast; sex-specific DMRs were over-represented in CpG islands, suggesting some difference in regulation between sex and immune-cell specificity. Both positive and negative correlations between cell-specific expression and methylation were observed, with negative correlation being more frequent. Our acquired immune cell- and sex- specific methylome and transcriptome profiles provide novel insight on their complex regulatory interactions, and may particularly contribute to research of immune-mediated diseases. RNA purified from isolated 5 cell subsets (monocyte, B cells, CD4 T cells, CD8 T cells and PBMCs) obtained from 6 healthy female donors
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Project description:DNA methylation has an impact on regulation of gene expression, however the relation between the two is complex. By performing an integrative analysis of the methylome and transcriptome of the four main circulating immune cell-subsets from healthy females, namely B cells, monocytes, CD4 and CD8 T cells, the relation between the two was characterized. In addition, in light of the known sex bias in the prevalence of several immune-mediated diseases, the female datasets were compared with similar public available male datasets. Immune subset-specific differentially methylated regions (DMRs) were found to be highly similar between males and females; however numerous sex-specific DMRs shared by the four leukocytes subsets were identified, most located on autosomal chromosomes. This provides a list of highly interesting candidate genes to be studied in diseases with sexual dimorphism like autoimmunity. Immune cell-specific DMRs were mainly located in the gene body and intergenic region, distant from CpG islands but overlapping with enhancer elements, thus indicating the importance of distal regulatory elements in leukocyte subsets. In contrast; sex-specific DMRs were over-represented in CpG islands, suggesting some difference in regulation between sex and immune-cell specificity. Both positive and negative correlations between cell-specific expression and methylation were observed, with negative correlation being more frequent. Our acquired immune cell- and sex- specific methylome and transcriptome profiles provide novel insight on their complex regulatory interactions, and may particularly contribute to research of immune-mediated diseases.
2016-07-01 | GSE71115 | GEO
Project description:DNA methylation has an impact on regulation of gene expression, however the relation between the two is complex. By performing an integrative analysis of the methylome and transcriptome of the four main circulating immune cell-subsets from healthy females, namely B cells, monocytes, CD4 and CD8 T cells, the relation between the two was characterized. In addition, in light of the known sex bias in the prevalence of several immune-mediated diseases, the female datasets were compared with similar public available male datasets. Immune subset-specific differentially methylated regions (DMRs) were found to be highly similar between males and females; however numerous sex-specific DMRs shared by the four leukocytes subsets were identified, most located on autosomal chromosomes. This provides a list of highly interesting candidate genes to be studied in diseases with sexual dimorphism like autoimmunity. Immune cell-specific DMRs were mainly located in the gene body and intergenic region, distant from CpG islands but overlapping with enhancer elements, thus indicating the importance of distal regulatory elements in leukocyte subsets. In contrast; sex-specific DMRs were over-represented in CpG islands, suggesting some difference in regulation between sex and immune-cell specificity. Both positive and negative correlations between cell-specific expression and methylation were observed, with negative correlation being more frequent. Our acquired immune cell- and sex- specific methylome and transcriptome profiles provide novel insight on their complex regulatory interactions, and may particularly contribute to research of immune-mediated diseases.
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Project description:The relationship between DNA methylation and gene expression is complex and elusive. To further elucidate these relations, we performed an integrative analysis of the methylome and transcriptome of 4 circulating immune cell subsets (B cells, monocytes, CD4(+), and CD8(+) T cells) from healthy females. Additionally, in light of the known sex bias in the prevalence of several immune-mediated diseases, the female datasets were compared with similar public available male data sets. Immune cell-specific differentially methylated regions (DMRs) were found to be highly similar between sexes, with an average correlation coefficient of 0.82; however, numerous sex-specific DMRs, shared by the cell subsets, were identified, mainly on autosomal chromosomes. This provides a list of highly interesting candidate genes to be studied in disorders with sexual dimorphism, such as autoimmune diseases. Immune cell-specific DMRs were mainly located in the gene body and intergenic region, distant from CpG islands but overlapping with enhancer elements, indicating that distal regulatory elements are important in immune cell specificity. In contrast, sex-specific DMRs were overrepresented in CpG islands, suggesting that the epigenetic regulatory mechanisms of sex and immune cell specificity may differ. Both positive and, more frequently, negative correlations between subset-specific expression and methylation were observed, and cell-specific DMRs of both interactions were associated with similar biological pathways, while sex-specific DMRs were linked to networks of early development or estrogen receptor and immune-related molecules. Our findings of immune cell- and sex-specific methylome and transcriptome profiles provide novel insight on their complex regulatory interactions and may particularly contribute to research of immune-mediated diseases.
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-07-01 | E-GEOD-71245 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
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Project description:Although Burkitt lymphomas and follicular lymphomas both have features of germinal center B cells, they are biologically and clinically quite distinct. Here we performed whole-genome bisulfite, genome and transcriptome sequencing in 13 IG-MYC translocation-positive Burkitt lymphoma, nine BCL2 translocation-positive follicular lymphoma and four normal germinal center B cell samples. Comparison of Burkitt and follicular lymphoma samples showed differential methylation of intragenic regions that strongly correlated with expression of associated genes, for example, genes active in germinal center dark-zone and light-zone B cells. Integrative pathway analyses of regions differentially methylated in Burkitt and follicular lymphomas implicated DNA methylation as cooperating with somatic mutation of sphingosine phosphate signaling, as well as the TCF3-ID3 and SWI/SNF complexes, in a large fraction of Burkitt lymphomas. Taken together, our results demonstrate a tight connection between somatic mutation, DNA methylation and transcriptional control in key B cell pathways deregulated differentially in Burkitt lymphoma and other germinal center B cell lymphomas.
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