STAT6-mediated displacement of polycomb by trithorax complex establishes long-term maintenance of GATA3 expression in T helper type 2 cells.
Polycomb group (PcG) and trithorax group (TrxG) complexes exert opposing effects on the maintenance of the transcriptional status of the developmentally regulated Hox genes. In this study, we show that activation of STAT6 induces displacement of the PcG complex by the TrxG complex at the upstream region of the gene encoding GATA3, a transcription factor essential for T helper type 2 (Th2) cell differentiation. Once Th2 cells differentiate, TrxG complex associated with the TrxG component Menin binds to the whole GATA3 gene locus, and this binding is required for the long-term maintenance of expression of GATA3 and Th2 cytokine. Thus, STAT6-mediated displacement of PcG by the TrxG complex establishes subsequent STAT6-independent maintenance of GATA3 expression in Th2 cells via the recruitment of the Menin-TrxG complex.
Onodera
Atsushi
A
Department of Immunology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan.
Yamashita
Masakatsu
M
Endo
Yusuke
Y
Kuwahara
Makoto
M
Tofukuji
Soichi
S
Hosokawa
Hiroyuki
H
Kanai
Akinori
A
Suzuki
Yutaka
Y
Nakayama
Toshinori
T
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D050990:GATA3 Transcription Factor / Q000096:biosynthesis* / Q000276:immunology; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D046912:Multiprotein Complexes / Q000276:immunology / Q000378:metabolism*; D063146:Polycomb-Group Proteins; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism; D012097:Repressor Proteins / Q000276:immunology / Q000378:metabolism*; D050800:STAT6 Transcription Factor / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology
D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; C484898:Men1 protein, mouse; D046912:Multiprotein Complexes; D063146:Polycomb-Group Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse