Loading…
Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells
Cell differentiation involves activation and silencing of lineage-specific genes. Here we show that the transcription factor Runx3 is induced in T helper type 1 (T H 1) cells in a T-bet-dependent manner, and that both transcription factors T-bet and Runx3 are required for maximal production of inter...
Saved in:
Published in: | Nature Immunology 2007-02, Vol.8 (2), p.145-153 |
---|---|
Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | Cell differentiation involves activation and silencing of lineage-specific genes. Here we show that the transcription factor Runx3 is induced in T helper type 1 (T
H
1) cells in a T-bet-dependent manner, and that both transcription factors T-bet and Runx3 are required for maximal production of interferon-γ (IFN-γ) and silencing of the gene encoding interleukin 4 (
Il4
) in T
H
1 cells. T-bet does not repress
Il4
in Runx3-deficient T
H
2 cells, but coexpression of Runx3 and T-bet induces potent repression in those cells. Both T-bet and Runx3 bind to the
Ifng
promoter and the
Il4
silencer, and deletion of the silencer decreases the sensitivity of
Il4
to repression by either factor. Our data indicate that cytokine gene expression in T
H
1 cells may be controlled by a feed-forward regulatory circuit in which T-bet induces Runx3 and then 'partners' with Runx3 to direct lineage-specific gene activation and silencing. |
---|---|
ISSN: | 1529-2908 1529-2916 1365-2567 |
DOI: | 10.1038/ni1424 |