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Series GSE57412 Query DataSets for GSE57412
Status Public on Jan 20, 2015
Title Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation [ChIP-Seq]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary DNA methylation is an epigenetic modification associated with transcriptional repression of promoters and is essential for mammalian development. Establishment of DNA methylation is mediated by the de novo DNA methyltransferases DNMT3A and DNMT3B, whereas DNMT1 ensures maintenance of methylation through replication. Absence of these enzymes is lethal, and somatic mutations in these genes have been associated with several human diseases. How genomic DNA methylation patterns are regulated remains poorly understood, as the mechanisms that guide recruitment and activity of DNMTs in vivo are largely unknown. To gain insights into this matter we determined chromosomal binding and site-specific activity of the mammalian de novo DNA methyltransferases DNMT3A and DNMT3B. We show that both enzymes localize to methylated, CpG dense regions in mouse stem cells, yet are excluded from active promoters and enhancers. By specifically measuring sites of de novo methylation, we observe that enzymatic activity reflects chromosomal binding. De novo methylation increases with CpG density, yet is excluded from nucleosomes. Notably, we observed selective binding of DNMT3B to the bodies of transcribed genes, which leads to their preferential methylation. This targeting to transcribed sequences requires SETD2-mediated methylation of lysine 36 on histone H3 and a functional PWWP domain of DNMT3B. Together these findings reveal how sequence and chromatin cues guide de novo methyltransferase activity to ensure methylome integrity.
 
Overall design Genome-wide binding analysis for biotin-tagged DNMT3A2 and DNMT3B and variants in wild type ES, wild type neuroprogenitor cells, ES cells triple-KO for Dnmt1,3a,3b and ES cell mutant for Setd2
 
Contributor(s) Baubec T, Schübeler D
Citation(s) 25607372
Submission date May 07, 2014
Last update date May 15, 2019
Contact name Dirk Schuebeler
Organization name Friedrich Miescher Institute for Biomedical Research
Street address Maulbeerstrasse 66
City Basel
ZIP/Postal code 4058
Country Switzerland
 
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (15)
GSM1382257 ES_DNMT3A2_rep1
GSM1382258 ES_DNMT3A2_rep2
GSM1382259 ES_DNMT3B1_rep1
This SubSeries is part of SuperSeries:
GSE57413 Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation
Relations
BioProject PRJNA246411
SRA SRP041761

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Supplementary file Size Download File type/resource
GSE57412_RAW.tar 360.4 Mb (http)(custom) TAR (of WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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