Transcriptional repression of the IL-2 gene in Th cells by ZEB.
Th1- and Th2-type cells mediate distinct effector functions via cytokine secretion in response to immunologic challenge. Precursor Th cells transcribe IFN-gamma, IL-2, and IL-4 upon activation. Repeated stimulation of Th precursor cells in the presence of IL-4 leads to terminally differentiated Th2 cells that have lost the ability to transcribe the IL-2 gene. We provide evidence that repression of IL-2 gene expression in Th2 cells and partial repression in Th1 cells are mediated by ZEB, a zinc finger, E box-binding transcription factor. This factor binds to a negative regulatory element, NRE-A, in the IL-2 promoter, thereby acting as a potent repressor of IL-2 transcription.
Yasui
D H
DH
Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, USA.
Genetta
T
T
Kadesch
T
T
Williams
T M
TM
Swain
S L
SL
Tsui
L V
LV
Huber
B T
BT
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D007376:Interleukin-2 / Q000235:genetics* / Q000276:immunology; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014157:Transcription Factors; D015533:Transcriptional Activation; D014162:Transfection; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D016376:Oligonucleotides, Antisense; D012097:Repressor Proteins; D014157:Transcription Factors