TY - JOUR
T1 - Cutting edge
T2 - GATA-3-dependent enhancer activity in IL-4 gene regulation
AU - Ranganath, Sheila
AU - Ouyang, Wenjun
AU - Bhattarcharya, Deepta
AU - Sha, William C.
AU - Grupe, Andrew
AU - Peltz, Gary
AU - Murphy, Kenneth M.
PY - 1998/10/15
Y1 - 1998/10/15
N2 - Previously, we analyzed the proximal IL-4 promoter in directing Th2- specific activity. An 800-base pair proximal promoter conferred some Th2- selective expression in transgenic mice. However, this region directed extremely low reporter mRNA levels relative to endogenous IL-4 mRNA, suggesting that full gene activity requires additional enhancer elements. Here, we analyzed large genomic IL-4 regions for enhancer activity and interaction with transcription factors. The proximal IL-4 promoter is only moderately augmented by GATA-3, but certain genomic regions significantly enhanced GATA-3 promoter transactivation. Some enhancing regions contained consensus GATA sites that hound Th2-specific complexes. However, retroviral transduction of GATA-3 into developing T cells induced IL-5 to full Th2 levels, but only partially restored IL-4 production. Thus, we propose that GATA-3 is permissive, but not sufficient, for full IL-4 enhancement and may act through GATA elements surrounding the IL-13/IL-4 gene locus.
AB - Previously, we analyzed the proximal IL-4 promoter in directing Th2- specific activity. An 800-base pair proximal promoter conferred some Th2- selective expression in transgenic mice. However, this region directed extremely low reporter mRNA levels relative to endogenous IL-4 mRNA, suggesting that full gene activity requires additional enhancer elements. Here, we analyzed large genomic IL-4 regions for enhancer activity and interaction with transcription factors. The proximal IL-4 promoter is only moderately augmented by GATA-3, but certain genomic regions significantly enhanced GATA-3 promoter transactivation. Some enhancing regions contained consensus GATA sites that hound Th2-specific complexes. However, retroviral transduction of GATA-3 into developing T cells induced IL-5 to full Th2 levels, but only partially restored IL-4 production. Thus, we propose that GATA-3 is permissive, but not sufficient, for full IL-4 enhancement and may act through GATA elements surrounding the IL-13/IL-4 gene locus.
UR - http://www.scopus.com/inward/record.url?scp=0032531544&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.161.8.3822
DO - 10.4049/jimmunol.161.8.3822
M3 - Article
C2 - 9780146
AN - SCOPUS:0032531544
SN - 0022-1767
VL - 161
SP - 3822
EP - 3826
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -