Prediction of regulatory transcription factors in T helper cell differentiation and maintenance.
Naive T-helper (Th) cells differentiate into distinct lineages including Th1, Th2, Th17 and regulatory T (Treg) cells. Each of these Th-lineages has specific functions in immune defense and T cell homeostasis. Th cell fate decisions and commitment are dependent on the kind and strength of T cell stimulation and the subsequent gene expression profiles. Our analysis targeted the identification of new regulatory transcription factor binding sites (TFBSs) in the promoter regions of up- and down-regulated genes in Treg cell differentiation and lineage maintenance. For this approach we compared different gene groups from global gene expression studies with background models of randomly selected genes to identify significantly overrepresented TFBSs. Results of our analysis suggest that Ets and IRF family members contribute to the regulation of the initial induction of Treg cells. Furthermore, we identified the overrepresented TFBS-pairs Runx-NFAT and GATA3-Foxp3 in Treg specific genes and Foxp3 dependent genes, respectively. Interestingly, previous studies have observed functional interactions of both TFBS-pairs in T cells. This study provides a starting point for further investigations to elucidate the transcriptional network in Treg cells.
Institute for Theoretical Biology, Humboldt University of Berlin, Invalidenstr. 43, 10115 Berlin, Germany. yuehien@gmail.com
Yue-Hien
YH
Lee
Manuela
M
Benary
Ria
R
Baumgrass
Hanspeter
H
Herzel
D002454:Cell Differentiation; D019295:Computational Biology; D050657:Core Binding Factor alpha Subunits / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D050657:Core Binding Factor alpha Subunits; D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor; D050778:NFATC Transcription Factors; D050796:STAT3 Transcription Factor; D014157:Transcription Factors