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PMID:20956546

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Citation

Onodera, A, Yamashita, M, Endo, Y, Kuwahara, M, Tofukuji, S, Hosokawa, H, Kanai, A, Suzuki, Y and Nakayama, T (2010) STAT6-mediated displacement of polycomb by trithorax complex establishes long-term maintenance of GATA3 expression in T helper type 2 cells. J. Exp. Med. 207:2493-506

Abstract

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.

Links

PubMed PMC2964576 Online version:10.1084/jem.20100760

Keywords

Animals; Cell Differentiation/physiology; GATA3 Transcription Factor/biosynthesis; GATA3 Transcription Factor/immunology; Gene Expression Regulation/physiology; Mice; Mice, Inbred BALB C; Multiprotein Complexes/immunology; Multiprotein Complexes/metabolism; Proto-Oncogene Proteins/immunology; Proto-Oncogene Proteins/metabolism; Repressor Proteins/immunology; Repressor Proteins/metabolism; STAT6 Transcription Factor/immunology; STAT6 Transcription Factor/metabolism; Th2 Cells/immunology; Th2 Cells/metabolism; Transcription, Genetic/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:MEN1

enables

GO:0043565: sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(MGI:MGI:95663)

Seeded From UniProt

complete

MOUSE:MEN1

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2158698

P

Seeded From UniProt

complete

MOUSE:IFNG

located_in

GO:0009897: external side of plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:IL4

located_in

GO:0009897: external side of plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:STAT6

acts_upstream_of_or_within

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(MGI:MGI:95663)

Seeded From UniProt

complete

MOUSE:EZH2

enables

GO:0043565: sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:SUZ12

enables

GO:0043565: sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:BMI1

enables

GO:0043565: sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:IFNG

part_of

GO:0009897: external side of plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:IL4

part_of

GO:0009897: external side of plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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