TY - JOUR
T1 - The Ets transcription factor ERM is Th1-specific and induced by IL-12 through a Stat4-dependent pathway
AU - Ouyang, Wenjun
AU - Jacobson, Nils G.
AU - Bhattacharya, Deepta
AU - Gorham, James D.
AU - Fenoglio, Domenic
AU - Sha, William C.
AU - Murphy, Theresa L.
AU - Murphy, Kenneth M.
PY - 1999/3/30
Y1 - 1999/3/30
N2 - Interleukin 12 (IL-12)-induced T helper 1 (Th1) development requires Stat4 activation. However, antigen-activated Th1 cells can produce interferon γ (IFN-γ) independently of IL-12 and Stat4 activation. Thus, in differentiated Th1 cells, factors regulated by IL-12 and Stat4 may be involved in IFN-γ production. Using subtractive cloning, we identified ERM, an Ets transcription factor, to be a Th1-specific, IL-12-induced gene. IL- 12-induction of ERM occurred in wild-type and Stat1-deficient, but not Stat4- deficient, T cells, suggesting ERM is Stat4-inducible. Retroviral expression of ERM did not restore IFN-γ production in Stat4-deficient T cells, but augmented IFN-γ expression in Stat4-heterozygous T cells. Ets factors frequently regulate transcription via cooperative interactions with other transcription factors, and ERM has been reported to cooperate with c-Jun. However, in the absence of other transcription factors, ERM augmented expression of an IFN-γ reporter by only 2-fold. Thus, determining the requirement for ERM in Th1 development likely will require gene targeting.
AB - Interleukin 12 (IL-12)-induced T helper 1 (Th1) development requires Stat4 activation. However, antigen-activated Th1 cells can produce interferon γ (IFN-γ) independently of IL-12 and Stat4 activation. Thus, in differentiated Th1 cells, factors regulated by IL-12 and Stat4 may be involved in IFN-γ production. Using subtractive cloning, we identified ERM, an Ets transcription factor, to be a Th1-specific, IL-12-induced gene. IL- 12-induction of ERM occurred in wild-type and Stat1-deficient, but not Stat4- deficient, T cells, suggesting ERM is Stat4-inducible. Retroviral expression of ERM did not restore IFN-γ production in Stat4-deficient T cells, but augmented IFN-γ expression in Stat4-heterozygous T cells. Ets factors frequently regulate transcription via cooperative interactions with other transcription factors, and ERM has been reported to cooperate with c-Jun. However, in the absence of other transcription factors, ERM augmented expression of an IFN-γ reporter by only 2-fold. Thus, determining the requirement for ERM in Th1 development likely will require gene targeting.
UR - http://www.scopus.com/inward/record.url?scp=0033616607&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033616607&partnerID=8YFLogxK
U2 - 10.1073/pnas.96.7.3888
DO - 10.1073/pnas.96.7.3888
M3 - Article
C2 - 10097133
AN - SCOPUS:0033616607
SN - 0027-8424
VL - 96
SP - 3888
EP - 3893
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 7
ER -