E-GEOD-27434 - Critical Requirement of the DNA Methyltransferase, Dnmt1, for the Development and Function of Foxp3+ Regulatory T Cells

Status
Released on 21 April 2013, last updated on 2 June 2014
Organism
Mus musculus
Samples (6)
Array (1)
Protocols (5)
Description
We investigated the role of DNMT1 in immune homeostasis by generating mice lacking DNMT1 in Foxp3+ T-regulatory (Treg) cells. These mice showed decreased peripheral Foxp3+ Tregs, complete loss of Foxp3+ Treg suppressive functions in vitro and in vivo, and died from autoimmunity by 3-4 weeks unless they received perinatal transfer of wild-type Tregs that prolonged their survival. Methylation of CpG-sites in the TSDR region of Foxp3 was unaffected by DNMT1 deletion, but microarray revealed more >500 proinflammatory and other genes were upregulated in DNMT1-/- Tregs. CD4-Cre-mediated DNMT1 deletion showed inability of conventional T cells to convert to Foxp3+ Treg under appropriate polarizing conditions. Hence, DNMT1 is absolutely necessary for maintenance of the gene program required for normal Treg development and function. RNA from three independent samples of magnetically separated CD4+CD25+ Treg of fl-DNMT1/Foxp3cre mice, compared to wild type (C57BL6) control
Experiment type
transcription profiling by array 
Contacts
Liqing Wang, Rongxiang Han, Tatiana Akimova, Tricia R Bhatti, Ulf H Beier, Wayne W Hancock, Yujie Liu
Citation
MIAME
PlatformsProtocolsFactorsProcessedRaw
Files
Investigation descriptionE-GEOD-27434.idf.txt
Sample and data relationshipE-GEOD-27434.sdrf.txt
Raw data (1)E-GEOD-27434.raw.1.zip
Processed data (1)E-GEOD-27434.processed.1.zip
Array designA-AFFY-36.adf.txt
Links