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Series GSE42396 Query DataSets for GSE42396
Status Public on Feb 01, 2013
Title Combined deficiency of Tet1 and Tet2 is compatible with development but leads to epigenetic instability
Organism Mus musculus
Experiment type Methylation profiling by high throughput sequencing
Summary Tet enzymes (Tet1/2/3) convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Tet1 and Tet2 mediate 5hmC generation in mouse embryonic stem cells (ESCs) and various embryonic and adult tissues. To investigate the effects of combined deficiency of Tet1 and Tet2 on pluripotency and development, we have generated Tet1 and Tet2 double knockout (DKO) ESCs and mice. DKO ESCs were depleted of 5hmC, but remained pluripotent with subtle defects in differentiation and changes in gene expression. Double mutant embryos and chimeras exhibited mid-gestation defects and postnatal DKO mice displayed partially penetrant neonatal lethality and stochastic perturbation of imprinting. Viable DKO animals developed normally to adulthood but had reduced 5hmC level, increased 5mC level and lacked 5hmC in germ cells. Nevertheless, DKO mice of both sexes were fertile with females having smaller ovaries and reduced fertility. Our data suggest that both Tet1 and Tet2 contribute to 5hmC levels during development. Their combined loss does not block differentiation and embryogenesis, but leads to partially penetrant embryonic and perinatal abnormalities and compromised viability. Moreover, the presence of substantial levels of 5hmC in DKO embryos and adult mice suggests a significant contribution of Tet3 in hydroxylation of 5mC during development.
Overall design Methylation patterns in tissue samples from a series of wt and Tet1/Tet2 DKO embryos, neonates and adults were generated using methylated DNA immunoprecipitation with antibodies against 5mC (MeDIP) and 5hmC (hMeDIP) followed by deep sequencing.
Contributor(s) Lyko F, Breiling A
Citation(s) 23352810
Submission date Nov 19, 2012
Last update date May 15, 2019
Contact name Guenter Raddatz
Organization name German Center for Cancer Research
Street address Im Neuenheimer Feld 580
City Heidelberg
ZIP/Postal code 69120
Country Germany
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (13)
GSM1039178 1_neonate-dko
GSM1039179 2_neonate-wt
GSM1039180 3_neonate-dko
BioProject PRJNA181954
SRA SRP017248

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE42396_RAW.tar 186.6 Mb (http)(custom) TAR (of BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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