Identification and characterization of SKAT-2, a novel Th2-specific zinc finger gene.
We have identified a novel Kruppel-type zinc finger (ZF) gene, SKAT-2, which is selectively expressed by murine Th2 cells. The protein encoded by this gene has 14 C2H2-type ZF tandemly arrayed at its C terminus and N-terminal SCAN box and KRAB domains. SKAT-2 is tissue restricted in expression at the RNA level, detectable only in brain and at low levels in kidney and spleen and few hematopoietic cell lines. By in situ hybridization, SKAT-2 expression was found to peak in antigen-stimulated CD4(+) T cells after 2-3 days of culture under Th2 but not Th1 biasing conditions. This pattern of expression closely mirrored that of GATA-3 in the same cells. In transient transfection experiments in phorbol 12-myristate 13-acetate/ionomycin-stimulated EL4 cells, SKAT-2 was found to up-regulate the activity of the IL-4 but not the IL-5 promoter, contrasting with the ability of GATA-3 to activate both promoters. This result was confirmed using clones of EL4 cells stably expressing an inducible form of SKAT-2, thus SKAT-2 is a novel Th2-specific gene that may play a role in selective regulation of cytokine genes in T cells.
Blanchard
A D
AD
Molecular Immunology Unit, Glaxo Wellcome R&D, Stevenage, GB. adb33949@GlaxoWellcome.co.uk
Page
K R
KR
Watkin
H
H
Hayward
P
P
Wong
T
T
Bartholomew
M
M
Quint
D J
DJ
Daly
M
M
Garcia-Lopez
J
J
Champion
B R
BR
D000595:Amino Acid Sequence; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology; D050990:GATA3 Transcription Factor; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D011506:Proteins / Q000235:genetics* / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D009419:Nerve Tissue Proteins; D011506:Proteins; D015534:Trans-Activators; C417530:Zfp287 protein, mouse