Mbd2 promotes Foxp3 demethylation and T-regulatory cell function
Transcriptomics Dataset
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General Information
AccessionGSE48653
TitleMbd2 promotes Foxp3 demethylation and T-regulatory cell function
DescriptionThe proposed use of Foxp3+ T-regulatory (Treg) cells as potential cellular therapy in patients with autoimmune diseases, or post-hemopoietic stem cell or organ transplantation, requires a sound understanding of the transcriptional regulation of Foxp3 expression. Conserved CpG dinucleotides in the Treg-specific demethylated region (TSDR) upstream of Foxp3 are demethylated only in stable, thymic-derived Foxp3+ Tregs. Since methyl-binding domain (Mbd) proteins recruit histone-modifying and chromatin-remodeling complexes to methylated sites, we tested whether targeting of Mbd2 might promote demethylation of Foxp3 and thereby promote Treg numbers or function. Surprisingly, while ChIP analysis showed Mbd2 binding to the Foxp3-associated TSDR site in Tregs, Mbd2 targeting by homologous recombination or siRNA decreased Treg numbers and impaired Treg suppressive function in vitro and in vivo. Moreover, we found complete TSDR demethylation in WT Tregs but >75%% methylation in Mbd2-/- Tregs, whereas re-introduction of Mbd2 into Mbd2-null Tregs restored TSDR demethylation, Foxp3 gene expression and Treg suppressive function. Lastly, Mbd2-/- Tregs had markedly binding of the DNA demethylase enzyme, Tet2, in the TSDR region. These data show that Mbd2 has a key role in promoting TSDR demethylation, Foxp3 expression and Treg suppressive function.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE48653
RepositoryGene Expression Omnibus
Tools used to analyze the dataset
Keyword
Dataset Accession
Enrichr
Published May 2016
A comprehensive gene set enrichment analysis web server 2016 update
7759
65
Characteristic Direction
Published March 2014
A geometrical multivariate approach to identify differentially expressed genes
26829
GeneMANIA
Published June 2010
Biological network integration for gene prioritization and predicting gene function
7435
L1000CDS2
Published August 2016
An ultra-fast LINCS L1000 Characteristic Direction signature search engine
7756
PAEA
Published November 2015
Enrichment analysis tool implementing the principal angle method
3879
Canned Analyses generated with the dataset
Filters  
Dataset Accession
Tool Name
Direction
Geneset
Small molecules which mimic MBD2 KO
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse MBD2 KO
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which rev...
Enrichment analysis of genes dysregulated in MBD2 KO
PAEA, Characteristic Direction
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Interaction network and enrichment analysis of genes downregulated in MBD2 KO
GeneMANIA, Characteristic Direction
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Interaction network and enrichment analysis of genes upregulated in MBD2 KO
GeneMANIA, Characteristic Direction
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Enrichment analysis of genes downregulated in MBD2 KO
Enrichr, Characteristic Direction
An enrichment analysis was performed on the top 500 most downregulated genes identified by...
Enrichment analysis of genes upregulated in MBD2 KO
Enrichr, Characteristic Direction
An enrichment analysis was performed on the top 500 most upregulated genes identified by a...
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