INTERFERON-GAMMA-INDUCED TRANSCRIPTION OF THE HIGH-AFFINITY FC RECEPTOR FOR IGG REQUIRES ASSEMBLY OF A COMPLEX THAT INCLUDES THE 91-KDA SUBUNIT OF TRANSCRIPTION FACTOR ISGF3
Rn. Pearse et al., INTERFERON-GAMMA-INDUCED TRANSCRIPTION OF THE HIGH-AFFINITY FC RECEPTOR FOR IGG REQUIRES ASSEMBLY OF A COMPLEX THAT INCLUDES THE 91-KDA SUBUNIT OF TRANSCRIPTION FACTOR ISGF3, Proceedings of the National Academy of Sciences of the United Statesof America, 90(9), 1993, pp. 4314-4318
A 39-nt DNA sequence, the interferon gamma (IFN-gamma) response region
(GRR), is necessary for the IFN-gamma-induced transcription of the hi
gh-affinity Fc receptor for IgG (FcgammaRI) and sufficient for the IFN
-gamma-induced transcription of transfected plasmids. By using extract
s from IFN-gamma-treated cells, three protein complexes will assemble
in vitro on a 9-nt core region in the 3' domain of the GRR. The sequen
ce of this core resembles the IFN-gamma-activated sequence (GAS) descr
ibed for the GBP gene. Mutations in this GAS core region prevent compl
ex assembly and result in the loss of IFN-gamma induction of reporter
constructs containing the mutation. In addition to the GAS core region
, a 5' region of the GRR is necessary for optimal IFN-gamma induction
and for formation of one of the DNA-protein complexes. By antibody rea
ctivity, we show that a 91-kDa protein, first identified as a componen
t of ISGF3, the IFN-alpha-induced transcription complex, is present in
at least two of the DNA-protein complexes. IFN-alpha can induce the f
ormation of the faster-migrating 91-kDa protein-GAS complex but not th
e slower-migrating complex. Furthermore, IFN-alpha does not result in
appreciable transcriptional activation of FcgammaRI or constructs cont
aining the GRR. Thus, these data demonstrate that the IFN-gamma-activa
ted 91-kDa protein is required for IFN-gamma induction of FcgammaRI an
d suggest that an additional complex may be required for optimal expre
ssion and specificity.