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Status |
Public on Nov 04, 2013 |
Title |
Dynamic changes of DNA methylome and hydroxymethylome during neural differentiation of hES cell (hMeDIP-Seq and MBD-Seq) |
Organism |
Homo sapiens |
Experiment type |
Methylation profiling by high throughput sequencing
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Summary |
DNA methylation and hydroxymethylation have been implicated in normal development and differentiation, but our knowledge about the genome-wide distribution of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) during cellular differentiation remains limited. Using in vitro model system of gradual differentiation of human embryonic stem (hES) cells into ventral midbrain-type neural precursor (NP) cells and terminally into dopamine (DA) neurons, we explored changes in 5mC or 5hmC patterns during lineage commitment. We used three techniques, 450K DNA methylation array, MBD-seq, and hMeDIP-seq, and found combination of these methods can provide comprehensive information on the genome-wide 5mC or 5hmC patterns. We observed dramatic changes of 5mC patterns during differentiation of hES cells into NP cells. Although genome-wide 5hmC distribution was more stable than 5mC, coding exons, CpG islands and shores showed dynamic 5hmC patterns during differentiation. In addition to the role of DNA methylation as a mechanism to initiating gene silencing, we also found DNA methylation as a locking system to maintain gene silencing. More than 1,000 genes including mesoderm development related genes acquired promoter methylation during neuronal differentiation even though they were already silenced in hES cells. Finally, we found that activated genes lost 5mC in transcription start site (TSS) but acquired 5hmC around TSS and gene body during differentiation. Our findings may provide clues for elucidating the molecular mechanisms underlying lineage specific differentiation of pluripotent stem cells during human embryonic development.
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Overall design |
Examination of hMeDIP-Seq and MBD-Seq in 3 cell types (human embryonic stem, neural precursor, and dopamine neuron cells)
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Contributor(s) |
Kim M, Park Y, Kang T, Lee S, Rhee Y, Park J, Kim HJ, Kim S, Lee D, Lee D, Kim YS |
Citation(s) |
24087792 |
Submission date |
May 24, 2012 |
Last update date |
Mar 22, 2019 |
Contact name |
Mirang Kim |
E-mail(s) |
mirnag@kribb.re.kr
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Organization name |
KRIBB(Korea Research Institute of Bioscience and Biotechnology
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Department |
Personalized Genomic Medicine Research Center
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Street address |
125 Gwahak-ro, Yuseong-gu
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City |
Daejeon |
ZIP/Postal code |
34141 |
Country |
South Korea |
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Platforms (1) |
GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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Samples (6)
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GSM936837 |
H9 ES-derived neural precursor cells 2 |
GSM936838 |
H9 ES-derived dopamine neuron cells 1 |
GSM936839 |
H9 ES-derived dopamine neuron cells 2 |
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This SubSeries is part of SuperSeries: |
GSE38217 |
Dynamic changes of DNA methylome and hydroxymethylome during neural differentiation of hES cells |
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Relations |
BioProject |
PRJNA167471 |
SRA |
SRP013367 |