Transcription Factors Ets2 and Sp1 Act Synergistically with Histone Acetyltrans-ferase p300 in Activating Human Interleukin-12 p40 Promoter

There has been considerable interest in researching the regulatory mechanisms that control thesynthesis of interleukin (IL)-12,which plays a central role in the differentiation of T-helper-1 cells.In thisstudy,we performed a series of transient transfection experiments designed to elucidate the functional rela-tionship between the IL-12 promoter-specific transcription factors (Ets2 and Sp1) and histone acetylationmodification in IL-12 regulation mediated by p300 and various histone deacetylases (HDACs).Results pre-sented in this report demonstrated that the transcription factors Ets2 and Sp1 acted synergistically with p300to activate the human IL-12 promoter.The histone acetyltransferase (HAT) activity of p300 was required forthis synergic effect,because the adenovirus E1A protein inhibited the synergy.Conversely,HDACs re-pressed the synergic effect of transcription factors and histone acetylation on the activation of IL-12,whilep300 was able to rectify it.These data indicated that Ets2 and Sp1 worked concertedly and synergisticallywith p300 in the regulation of human IL-12 expression.