Transcription factors Ets2 and Sp1 act synergistically with histone acetyltransferase p300 in activating human interleukin-12 p40 promoter.
There has been considerable interest in researching the regulatory mechanisms that control the synthesis of interleukin (IL)-12, which plays a central role in the differentiation of T-helper-1 cells. In this study, we performed a series of transient transfection experiments designed to elucidate the functional relationship between the IL-12 promoter-specific transcription factors (Ets2 and Sp1) and histone acetylation modification in IL-12 regulation mediated by p300 and various histone deacetylases (HDACs). Results presented in this report demonstrated that the transcription factors Ets2 and Sp1 acted synergistically with p300 to activate the human IL-12 promoter. The histone acetyltransferase (HAT) activity of p300 was required for this synergic effect, because the adenovirus E1A protein inhibited the synergy. Conversely, HDACs repressed the synergic effect of transcription factors and histone acetylation on the activation of IL-12, while p300 was able to rectify it. These data indicated that Ets2 and Sp1 worked concertedly and synergistically with p300 in the regulation of human IL-12 expression.
Sun
Hai-Jing
HJ
Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
Xu
Xin
X
Wang
Xiu-Li
XL
Wei
Liang
L
Li
Fen
F
Lu
Jun
J
Huang
Bai-Qu
BQ
D002478:Cells, Cultured; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000502:physiology*; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics* / Q000378:metabolism; D053762:Interleukin-12 Subunit p40; D007668:Kidney / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D021122:Protein Subunits / Q000235:genetics* / Q000378:metabolism; D050787:Proto-Oncogene Protein c-ets-2 / Q000235:genetics / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D050787:Proto-Oncogene Protein c-ets-2; D016329:Sp1 Transcription Factor; D018664:Interleukin-12; D051548:Histone Acetyltransferases