GATA-binding protein-3 regulates T helper type 2 cytokine and ifng loci through interaction with metastasis-associated protein 2.
GATA-binding protein-3 (GATA-3) regulates the T helper type 2 (Th2) cytokine locus through induction of chromatin remodelling. However, the molecular mechanism for this is poorly understood. To understand this mechanism better, we screened GATA-3 interacting proteins using affinity purification and mass spectrometry. We found that GATA-3 bound to metastasis-associated protein 2 (MTA-2), a component of the NuRD chromatin remodelling complex. GATA-3 and MTA-2 in turn bound to several regulatory regions of the Th2 cytokine locus and the ifng promoter. Cell transfection assay showed that MTA-2 acted as an antagonist with GATA-3 in the expression of Th2 cytokines, but co-operated with GATA-3 in the repression of the ifng gene expression. These results suggest that GATA-3 interacts with MTA-2 to co-ordinately regulate Th2 cytokine and ifng loci during T helper cell differentiation.
Hwang
Soo Seok
SS
Department of Life Science, Sogang University, Seoul, Korea.
Lee
Sumin
S
Lee
Wonyong
W
Lee
Gap Ryol
GR
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology* / Q000378:metabolism; D014162:Transfection
D016207:Cytokines; D050990:GATA3 Transcription Factor; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; D007371:Interferon-gamma