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Series GSE234028 Query DataSets for GSE234028
Status Public on Jun 30, 2023
Title Target capture bisulfite sequencing (tcBS-seq) to evaluate clonal methylation inheritance [BiSulfite-seq]
Organism Mus musculus
Experiment type Methylation profiling by high throughput sequencing
Summary DNA methylation is considered a stable epigenetic mark due to its presumed long-term inheritance through cell divisions. Here, we perform high-throughput bisulfite sequencing on clonally derived cell lines to quantitatively measure mitotic methylation inheritance at the nucleotide level. We find that although DNA methylation is generally faithfully maintained at hypo- and hypermethylated sites, this is not the case at intermediately methylated CpGs. Low fidelity intermediate methylation is interspersed throughout the genome and within genes with no or low transcriptional activity. Moreover, we determine that the probabilistic changes that occur at intermediately methylated sites are due to DNMT1 rather than DNMT3A/3B activity. The observed lack of clonal inheritance at intermediately methylated sites challenges the concept of DNA methylation as a consistently stable epigenetic mark.
 
Overall design To test whether DNMT3A/3B are mechanistically responsible for the probabilistic gain of methylation at intermediately methylated CpG sites, we generated four MEF lines (A, B, C, and D) from sibling E13.5 Dnmt3aflox/flox3bflox/flox mouse embryos and used recombinant TAT-CRE protein to induce the double knockout (DKO) in vitro. We subsequently performed tcBS-seq with four DKO and four matched control cell lines.
 
Contributor(s) Hay AD, Kessler NJ, Gebert D, Takahashi N, Tavares H, Teixeira FK, Ferguson-Smith AC
Citation(s) 37660134
Submission date Jun 02, 2023
Last update date Sep 15, 2023
Contact name Anne Ferguson-Smith
E-mail(s) afsmith@gen.cam.ac.uk
Organization name Cambridge University
Department Genetics
Street address 20 Downing Place
City Cambridge
ZIP/Postal code CB2 3EJ
Country United Kingdom
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (8)
GSM7441374 Primary MEF cells, population A, control (no TAT-CRE)
GSM7441375 Primary MEF cells, population B, control (no TAT-CRE)
GSM7441376 Primary MEF cells, population C, control (no TAT-CRE)
This SubSeries is part of SuperSeries:
GSE234695 Target capture bisulfite sequencing (tcBS-seq) to evaluate clonal methylation inheritance
Relations
BioProject PRJNA979209

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Supplementary file Size Download File type/resource
GSE234028_RAW.tar 194.2 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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