DNA methylation and gene expression changes during human embryonic stem cell differentiation
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE32371 | GEO | 2011/09/26
SECONDARY ACCESSION(S): PRJNA147971
REPOSITORIES: GEO
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Project description:Investigate the genome-wide DNA methylation and gene expression changes during human embryonic stem cell differentiation. hESCs (H1 and H13) DNA samples for 3 different differentian stage (D0, undifferentiated;D21, 21 days after undirected differentiation; D90, 90 days after undirected differentiation); two-color experiment, paired comparison (differentiated vs undifferentiated; A & B: two biological replicates). Differentian-stage variation in methylation profiling of human DNA samples were detected by MSAM. 2µg of DNA was serially digested with SmaI and XmaI followed by an adaptor ligation and adaptor mediated PCR amplification. Analysis of differentian-stage variation in gene expression of human mRNA samples were implementd following standard Agilent protocol.
2011-09-25 | E-GEOD-32371 | biostudies-arrayexpress
Project description:Purpose: we aimed to gain a genome-wide view of the dynamics in DNA methylation inheritance and define the factors associated with methylation fidelity. Methods: Using mouse embryonic stem cell (ES-E14TG2a) in both undifferentiated and differentiated states as a model system, we exploited the hairpin bisulfite sequencing approach to generate methylation data for DNA double strands simultaneously at single-base resolution. We generated the genome-wide hairpin bisulfite sequencing data to capture the methylation pattern variation during the stem cell transition from self-renewal to commitment, and integrated with various M-bM-^@M-^\omicsM-bM-^@M-^] data to scrutinize the relationships among DNA methylation inheritance, gene expression, histone modification, transcriptional factor binding and distribution of 5-hydroxylmethylation cytosine. Results and conclusion: Our results indicated that DNA methylation fidelity increases globally during early mouse embryonic stem cell differentiation. Methylation fidelity is remarkably high in promoter regions of actively expressed genes and positively correlated with active histone modification marks and binding of transcriptional factors. Strikingly, methylation fidelity follows a bimodal distribution for the intermediately methylated CpG dyads. In addition, the methylation difference in between two DNA strands rather than different DNA molecules is a major source of the intermediate DNA methylation. Lastly, while 5-hmC and 5-mC tend to coexist, no significant increase in the pairing with unmethylated cytosine was observed. For mouse embryonic stem cell of undifferentiated and spontaneous differentiated states, we determined DNA double strands methylation pattern by hairpin bisulfite sequencing approach and determined gene expression profiles using RNA-seq.
2014-05-12 | E-GEOD-48229 | biostudies-arrayexpress
Project description:Purpose: we aimed to gain a genome-wide view of the dynamics in DNA methylation inheritance and define the factors associated with methylation fidelity. Methods: Using mouse embryonic stem cell (ES-E14TG2a) in both undifferentiated and differentiated states as a model system, we exploited the hairpin bisulfite sequencing approach to generate methylation data for DNA double strands simultaneously at single-base resolution. We generated the genome-wide hairpin bisulfite sequencing data to capture the methylation pattern variation during the stem cell transition from self-renewal to commitment, and integrated with various “omics” data to scrutinize the relationships among DNA methylation inheritance, gene expression, histone modification, transcriptional factor binding and distribution of 5-hydroxylmethylation cytosine. Results and conclusion: Our results indicated that DNA methylation fidelity increases globally during early mouse embryonic stem cell differentiation. Methylation fidelity is remarkably high in promoter regions of actively expressed genes and positively correlated with active histone modification marks and binding of transcriptional factors. Strikingly, methylation fidelity follows a bimodal distribution for the intermediately methylated CpG dyads. In addition, the methylation difference in between two DNA strands rather than different DNA molecules is a major source of the intermediate DNA methylation. Lastly, while 5-hmC and 5-mC tend to coexist, no significant increase in the pairing with unmethylated cytosine was observed.
2014-05-12 | GSE48229 | GEO
Project description:In mammals, cellular identity is defined through strict regulation of chromatin modifications and DNA methylation that control gene expression. Methylation of cytosines at CpG sites in the genome is mainly associated with suppression; however, the reason for enhancer-specific methylation is not fully understood. We used sequential ChIP-bisulfite-sequencing for H3K4me1 and H3K27ac histone marks. By collecting data from the same genomic region, we identified enhancers differentially methylated between these two marks. We observed a global gain of CpG methylation primarily in H3K4me1-marked nucleosomes during mouse embryonic stem cell differentiation. This gain occurred largely in enhancer regions that regulate genes critical for differentiation. The higher levels of DNA methylation in H3K4me1- versus H3K27ac-marked enhancers, despite it being the same genomic region, indicates cellular heterogeneity of enhancer states. Analysis of single-cell RNA-seq profiles demonstrated that this heterogeneity correlates with gene expression during differentiation. Furthermore, heterogeneity of enhancer methylation correlates with transcription start site methylation. Our results provide insights into enhancer-based functional variation in complex biological systems.
| S-EPMC8062104 | biostudies-literature
Project description:BackgroundEnvironmental challenges during development affect the fetal epigenome, but the period(s) vulnerable to epigenetic dysregulation is(are) not clear. By employing a soy phytoestrogen, genistein, that is known to alter the epigenetic states of the A(vy) allele during embryogenesis, we have explored the sensitive period for epigenetic regulation. The post-implantation period, when de novo DNA methylation actively proceeds, is amenable to in vitro analysis using a mouse embryonic stem (ES) cell differentiation system.Methods and findingsMouse ES cells were differentiated in the presence or absence of genistein, and DNA methylation patterns on day 10 were compared by microarray-based promoter methylation analysis coupled with a methylation-sensitive endonuclease (HpaII/McrBC)-dependent enrichment procedure. Moderate changes in methylation levels were observed in a subset of promoters following genistein treatment. Detailed investigation of the Ucp1 and Sytl1 promoters further revealed that genistein does not affect de novo methylation occurring between day 0 and day 4, but interferes with subsequent regulatory processes and leads to a decrease in methylation level for both promoters.ConclusionGenistein perturbed the methylation pattern of differentiated ES cells after de novo methylation. Our observations suggest that, for a subset of genes, regulation after de novo DNA methylation in the early embryo may be sensitive to genistein.
| S-EPMC3084807 | biostudies-literature
Project description:m6A is the most abundant modification of mRNA in mammals and plays an important role in human development and disease. METTL14 is a key component of m6A methyltransferase complex. The project showed that its post-translational arginine methylation can regulate the generation of m6A and the endoderm differentiation of mouse embryonic stem cells, indicating its essential function in the normal development of embryos.
2021-05-17 | PXD018458 |
Project description:It has been reported that hypomagnetic fields (HMFs) have a negative influence on mammalian physiological functions. We previously reported that HMFs were detrimental to cell fate changes during reprogramming into pluripotency. These studies led us to investigate whether HMFs affect cell fate determination during direct differentiation. Here, we found that an HMF environment attenuates differentiation capacity and is detrimental to cell fate changes during the in vitro differentiation of embryonic stem cells (ESCs). Moreover, HMF conditions cause abnormal DNA methylation through the dysregulation of DNA methyltransferase3b (Dnmt3b) expression, eventually resulting in incomplete DNA methylation during differentiation. Taken together, these results suggest that an appropriate electromagnetic field (EMF) environment may be essential for favorable epigenetic remodeling during cell fate determination via differentiation.
| S-EPMC6361932 | biostudies-literature
Project description:The faithful transmission of DNA methylation patterns through cell divisions is essential for the daughter cells to retain a proper cell identity. To achieve a comprehensive assessment of methylation fidelity, we implemented a genome-scale hairpin bisulfite sequencing approach to generate methylation data for DNA double strands simultaneously. We show here that methylation fidelity increases globally during differentiation of mouse embryonic stem cells (mESCs), and is particularly high in the promoter regions of actively expressed genes and positively correlated with active histone modification marks and binding of transcription factors. The majority of intermediately (40%-60%) methylated CpG dinucleotides are hemi-methylated and have low methylation fidelity, particularly in the differentiating mESCs. While 5-hmC and 5-mC tend to coexist, there is no significant correlation between 5-hmC levels and methylation fidelity. Our findings may shed new light on our understanding of the origins of methylation variations and the mechanisms underlying DNA methylation transmission.
| S-EPMC4120083 | biostudies-literature
Project description:DNA methylation changes dynamically during development and is essential for embryogenesis in mammals. However, how DNA methylation affects developmental gene expression and cell differentiation remains elusive. During embryogenesis, many key transcription factors are used repeatedly, triggering different outcomes depending on the cell type and developmental stage. Here, we report that DNA methylation modulates transcription-factor output in the context of cell differentiation. Using a drug-inducible Gata4 system and a mouse embryonic stem (ES) cell model of mesoderm differentiation, we examined the cellular response to Gata4 in ES and mesoderm cells. The activation of Gata4 in ES cells is known to drive their differentiation to endoderm. We show that the differentiation of wild-type ES cells into mesoderm blocks their Gata4-induced endoderm differentiation, while mesoderm cells derived from ES cells that are deficient in the DNA methyltransferases Dnmt3a and Dnmt3b can retain their response to Gata4, allowing lineage conversion from mesoderm cells to endoderm. Transcriptome analysis of the cells' response to Gata4 over time revealed groups of endoderm and mesoderm developmental genes whose expression was induced by Gata4 only when DNA methylation was lost, suggesting that DNA methylation restricts the ability of these genes to respond to Gata4, rather than controlling their transcription per se. Gata4-binding-site profiles and DNA methylation analyses suggested that DNA methylation modulates the Gata4 response through diverse mechanisms. Our data indicate that epigenetic regulation by DNA methylation functions as a heritable safeguard to prevent transcription factors from activating inappropriate downstream genes, thereby contributing to the restriction of the differentiation potential of somatic cells.
| S-EPMC3694845 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series: GSE32080: DNA methylation profiling of embryonic stem cell differentiation into the three germ layers [MeDIP analysis] GSE32081: DNA methylation profiling of embryonic stem cell differentiation into the three germ layers [Expression analysis] Refer to individual Series
2012-02-15 | E-GEOD-32082 | biostudies-arrayexpress