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Series GSE142834 Query DataSets for GSE142834
Status Public on Jul 07, 2020
Title Structural basis of epigenetic protection of mouse lymphoid progenitor cells by Dnmt1 [Mouse WGBS]
Organism Mus musculus
Experiment type Methylation profiling by high throughput sequencing
Summary DNA methylation is a universal epigenetic mechanism involved in regulation of gene expression and genome stability. The DNA maintenance methylase DNMT1 ensures that DNA methylation patterns are faithfully transmitted to daughter cells during cell division. Because DNMT1 is essential for cell viability, little is known about its tissue-specific function. To overcome this impediment, forward genetic screens were conducted in medaka and zebrafish to identify viable dnmt1 alleles. The recovered recessive missense mutations lead to distorted structures of the catalytic pocket and reduced enzymatic activities, resulting in hypomethylation of genomic DNA that specifically impairs lymphoid development. The insights gleaned from fish dnmt1 alleles enabled the structure-guided generation of a hypomorphic variant of mouse Dnmt1, which also causes cell-autonomous defects of lymphoid development. The similar phenotypes observed in three distinct species suggest that the unique sensitivity of lymphocytes to perturbations of DNA methylation patterns is an evolutionarily conserved feature of all vertebrates. 
Overall design Forward genetic screens in zebrafish and medaka identified missense mutations in maintenance DNA methylase Dnmt1 specifically affecting lymphoid development. To examine the molecular consequences of these hypomorphic mutations, DNA methylatio9n levels were assessed in selected regions of the genomes. Based on structural analyses of fish Dnmt1 mutant proteins, a specific Dnmt1 mutation was also generated in mice. This led to hypomethylation of genomic DNA in lineage-negative cells of the bone marrow; additionally, the transcriptomes of several subtypes of hematopoietic progenitor cells (HSC; MPP1; MPP4) were compared by RNA-seq.
Contributor(s) Iwanami N, Sikora KO, Boehm T
Citation(s) 32585597
Submission date Jan 02, 2020
Last update date Jul 07, 2020
Contact name Thomas Boehm
Organization name MPI-IE Freiburg
Department Immunology
Street address Stübeweg 51
City Freiburg im Breisgau
ZIP/Postal code 79108
Country Germany
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (12)
GSM4240770 bone marrow progenitors, control rep1 (TruSeqMeth)
GSM4240771 bone marrow progenitors, control rep2 (TruSeqMeth)
GSM4240772 bone marrow progenitors, control rep3 (TruSeqMeth)
This SubSeries is part of SuperSeries:
GSE98648 Structural basis of epigenetic protection of mouse lymphoid progenitor cells by Dnmt1
BioProject PRJNA598572
SRA SRP239280

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Supplementary file Size Download File type/resource
GSE142834_HSC_hypermethylated_metileneDMRs.tsv.gz 571 b (ftp)(http) TSV
GSE142834_HSC_hypomethylated_metileneDMRs.tsv.gz 2.1 Mb (ftp)(http) TSV
GSE142834_HSC_metileneDMR_aggregate_methylation_values.tsv.gz 2.6 Mb (ftp)(http) TSV
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Processed data are available on Series record

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