60-kDa Tat-interactive protein (TIP60) positively regulates Th-inducing POK (ThPOK)-mediated repression of eomesodermin in human CD4+ T cells.
J Biol Chem
; 288(22): 15537-46, 2013 May 31.
Article
in En
| MEDLINE
| ID: mdl-23609452
ABSTRACT
The abundant expression of IFNγ in Th-inducing POK (ThPOK)-deficient CD4(+) T cells requires the activation of Eomesodermin (Eomes); however, the underlying mechanism of this phenomenon remains unclear. Here we report that ThPOK binds directly to the promoter region of the Eomes gene to repress its expression in CD4(+) T cells. We identified the histone acetyltransferase TIP60 as a co-repressor of ThPOK-target genes, where ectopically expressed TIP60 increased ThPOK protein stability by promoting its acetylation at its Lys(360) residue to then augment the transcriptional repression of Eomes. Moreover, knockdown of endogenous TIP60 abolished the stabilization of ThPOK in CD4(+) T cells, which led to the transcriptional activation of Eomes and increased production of IFNγ. Our results reveal a novel pathway by which TIP60 and ThPOK synergistically suppresses Eomes function and IFNγ production, which could contribute to the regulation of inflammation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Repressor Proteins
/
Transcription Factors
/
CD4-Positive T-Lymphocytes
/
Gene Expression Regulation
/
T-Box Domain Proteins
/
DNA-Binding Proteins
/
Histone Acetyltransferases
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
J Biol Chem
Year:
2013
Document type:
Article
Affiliation country:
China