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Series GSE38306 Query DataSets for GSE38306
Status Public on Aug 01, 2012
Title Promoter DNA methylation couples genome-defense mechanisms to epigenetic reprogramming in the mouse germline (part 2)
Organism Mus musculus
Experiment type Expression profiling by array
Summary Mouse primordial germ cells (PGCs) erase global DNA methylation (5mC) as part of the comprehensive epigenetic reprogramming that occurs during PGC development. 5mC plays an important role in maintaining stable gene silencing and repression of transposable elements (TE) but it is not clear how the extensive loss of DNA methylation impacts on gene expression and TE repression in developing PGCs. Using a novel epigenetic disruption and recovery screen and genetic analyses, we identified a core set of germline-specific genes that are dependent exclusively on promoter DNA methylation for initiation and maintenance of developmental silencing. These gene promoters appear to possess a specialised chromatin environment that does not acquire any of the repressive H3K27me3, H3K9me2, H3K9me3 or H4K20me3 histone modifications when silenced by DNA methylation. Intriguingly, this methylation-dependent subset is highly enriched in genes with roles in suppressing TE activity in germ cells. We show that the mechanism for developmental regulation of the germline genome-defence genes involves DNMT3B-dependent de novo DNA methylation. These genes are then activated by lineage-specific promoter demethylation during distinct global epigenetic reprogramming events in migratory (~E8.5) and post-migratory (E10.5-E11.5) PGCs. We propose that genes involved in genome defence are developmentally regulated exclusively by promoter DNA methylation as a sensory mechanism that is coupled to the potential for TE activation during global 5mC erasure, thereby acting as a failsafe to ensure TE suppression and maintain genomic integrity in the germline.
Overall design Total RNA isolated from control p53-/- or sample Dnmt1-/- (p53-/-) mouse embryonic fibroblasts
Contributor(s) Hackett JA
Citation(s) 22949617
Submission date May 29, 2012
Last update date Jun 14, 2018
Contact name Jamie Hackett
Organization name Gurdon Institue
Street address Tennis Court Road
City Cambridge
ZIP/Postal code CB2 1QN
Country United Kingdom
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (2)
GSM938428 p53-/-
GSM938429 Dnmt1-/- (p53-/-)
This SubSeries is part of SuperSeries:
GSE38307 Promoter DNA methylation couples genome-defense mechanisms to epigenetic reprogramming in the mouse germline
BioProject PRJNA167640

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE38306_RAW.tar 3.1 Mb (http)(custom) TAR
GSE38306_non-normalized.txt.gz 471.1 Kb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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