GA binding protein regulates interleukin 7 receptor alpha-chain gene expression in T cells
Authors:
Xue HH, Bollenbacher J, Rovella V, Tripuraneni R, Du YB, Liu CY, Williams A, McCoy JP and Leonard WJ
In:
Source:
Nat Immunol
Publication Date:
(
2004
)
Issue:
5(10)
:
1036-1044
Research Area:
Immunotherapy / Hematology
Cells used in publication:
PBMC, human
Species: human
Tissue Origin: blood
Platform:
Nucleofector® I/II/2b
Experiment
Primary human peripheral blood mononuclear cells were transfected by nucleofection with plasmids expressing siRNA to GABP. The cells were cotransfected with an EYFP expression plasmid to be able to select for transfected (i.e. knockdown cells) by FACS, facilitating subsequent knockdown analysis on the mRNA level by RT-RCR.
Abstract
The interleukin 7 receptor alpha-chain (IL-7Ralpha) is essential for T cell development in both humans and mice and for B cell development in mice. Whereas the transcription factor PU.1 regulates IL-7Ralpha expression in mouse pro-B cells via a GGAA motif, we demonstrate here that GA binding protein (GABP) bound to this site and was essential in the regulation of IL-7Ralpha expression in T cells, where PU.1 is not expressed. Moreover, IL-7Ralpha expression was diminished substantially in thymocytes but was normal on B220(+) fetal liver cells from mouse embryos with diminished expression of GABPalpha. Thus, GABP is essential for the regulation of IL-7Ralpha expression in T cells, and the differential regulation of IL-7Ralpha in distinct lymphoid lineages is achieved at least in part by differential recruitment of factors to the same GGAA motif.
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