Unknown,Transcriptomics,Genomics,Proteomics

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Comparison of genome-wide DNA methylation in MEFs derived from wildtype or estrogen receptor beta null mice using reduced representation bisulfite sequencing

ABSTRACT: Estrogen receptor beta (ERÎ²) is a ligand inducible transcription factor regulating gene expression in response to the female sex hormone estrogen. Previously, we found that ERÎ² deficiency results in changes in DNA methylation patterns at two gene promoters, implicating an involvement of ERÎ² in DNA methylation. In this study, we set out to explore this involvement on a genome-wide level, and to investigate the underlying mechanisms of this function. Using reduced representation bisulfite sequencing (RRBS), we compared genome-wide DNA methylation in mouse embryonic fibroblasts (MEFs) derived from wildtype (wt) and ERÎ² knock-out (Î²erko) mice, and identified around 8000 differentially methylated positions (DMPs). This suggests that ERÎ² is involved in regulating DNA methylation at specific sites in the genome. Genome-wide DNA methylation was analysed in MEFs derived from wildtype and ERbeta null mice by educed representation bisulfite sequencing (RRBS) on an Illumina Genome Analyser IIx platform.

ORGANISM(S): Mus musculus

SUBMITTER: JoÃ«lle RÃ¼egg

PROVIDER: E-GEOD-72230 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Oestrogen receptor β regulates epigenetic patterns at specific genomic loci through interaction with thymine DNA glycosylase.

Liu Yun Y Duong William W Krawczyk Claudia C Bretschneider Nancy N Borbély Gábor G Varshney Mukesh M Zinser Christian C Schär Primo P Rüegg Joëlle J

Epigenetics & chromatin 20160216

<h4>Background</h4>DNA methylation is one way to encode epigenetic information and plays a crucial role in regulating gene expression during embryonic development. DNA methylation marks are established by the DNA methyltransferases and, recently, a mechanism for active DNA demethylation has emerged involving the ten-eleven translocator proteins and thymine DNA glycosylase (TDG). However, so far it is not clear how these enzymes are recruited to, and regulate DNA methylation at, specific genomic ...[more]

PMID: 26889208

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Project description:We conducted a genome-wide DNA methylation analysis in CD19+ B-cells from CLL patient and normal control samples using reduced representation bisulfite sequencing (RRBS). The methylation status of 1.8-2.3 million CpGs in the CLL genome was determined; about 45% of these CpGs were located in more than 23,000 CpG islands (CGIs). While global CpG methylation was similar between CLL and normal B-cells, 1764 gene promoters were identified as being differentially methylated between the two groups. Aberrant hypermethylation was found in all HOX gene clusters and a significant number of WNT signaling pathway genes. The genes that were frequently hypermethylated were typically associated with histone H3 lysine 27 tri-methylation or bivalent domains in normal B-cells. An additional 152 genes were found to be differentially methylated between normal naïve and memory B-cells. Of these 152 genes, 123 were hypomethylated in memory B-cells when compared to naïve B-cells. Overall, CLL B-cells had methylation patterns more similar to memory B-cells than naïve B-cells. Cluster analysis showed that the tissue-specific methylated genes separated CLL samples into two groups with differential ZAP70 methylation status. Hypomethylation occurred more frequently in the gene body including introns, exons, and 3'-UTRs in CLL. The hypomethylation in the NFATc1 P2 promoter and first intron correlated with up-regulation of both NFATc1 RNA and protein expression levels in CLL suggesting that an epigenetic mechanism is involved in the constitutive activation of NFAT activity in CLL cells. This comprehensive DNA methylation map will further our understanding of the epigenetic contribution to cellular dysfunction in CLL. To perform a genome-wide analysis of DNA methylation in CLL, we applied the Reduced Representation Bisulfite Sequencing (RRBS) to CD19+ B-cells isolated from normal control and CLL peripheral blood samples. The genomic DNA from each sample was digested with the methylation-insensitive restriction enzyme MspI (restriction site, CCGG) and ligated to Illumina sequencing adaptors containing methylated cytosine residues. The ligated MspI fragments were size-selected, treated with sodium bisulfite, and amplified by PCR. The PCR products were purified and sequenced using Illumina GAIIx sequencer with a read length of 52 or 76bp. 11 CLL B-cell samples, 3 normal control samples including one each of normal CD19+, CD19+/ IgD+ naïve, and CD19+/CD27+ memory B-cell sample and three CLL cell lines (Mec-1, Mec-2, and Wac-3) were used. We generated 20-30 million Illumina sequencing reads for each sample.

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Dataset Information

Comparison of genome-wide DNA methylation in MEFs derived from wildtype or estrogen receptor beta null mice using reduced representation bisulfite sequencing

Publications

Oestrogen receptor β regulates epigenetic patterns at specific genomic loci through interaction with thymine DNA glycosylase.

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