Lefebvre Bruno, Ozato Keiko, Lefebvre Philippe
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
EMBO Rep. 2002 Apr;3(4):335-40. doi: 10.1093/embo-reports/kvf066. Epub 2002 Mar 15.
Ligand-dependent transcriptional activation of retinoic acid receptors (RARs) is a multistep process culminating in the formation of a multimeric co-activator complex on regulated promoters. Several co-activator complexes harbor an acetyl transferase activity, which is required for retinoid-induced transcription of reporter genes. Using murine P19 embryonal carcinoma cells, we examined the relationship between histone post-translational modifications and activation of the endogenous RARbeta2 promoter, which is under the control of a canonical retinoic acid response element and rapidly induced upon retinoid treatment. While histones H3 and H4 were constitutively acetylated at this promoter, retinoid agonists induced a rapid phosphorylation at Ser10 of histone H3. A retinoid antagonist, whose activity was independent of co-repressor binding to RAR, could oppose this agonist-induced H3 phosphorylation. Since such post-translational modifications were not observed at several other promoters, we conclude that histone H3 phosphorylation may be a molecular signature of the activated, retinoid-controlled mRARbeta2 gene promoter.
视黄酸受体（RARs）的配体依赖性转录激活是一个多步骤过程，最终在受调控的启动子上形成多聚体共激活因子复合物。几种共激活因子复合物具有乙酰转移酶活性，这是类维生素A诱导报告基因转录所必需的。利用小鼠P19胚胎癌细胞，我们研究了组蛋白翻译后修饰与内源性RARβ2启动子激活之间的关系，该启动子受典型视黄酸反应元件的控制，并在类维生素A处理后迅速诱导。虽然组蛋白H3和H4在该启动子上持续乙酰化，但类维生素A激动剂诱导组蛋白H3的Ser10迅速磷酸化。一种视黄酸拮抗剂，其活性独立于共抑制因子与RAR的结合，可对抗这种激动剂诱导的H3磷酸化。由于在其他几个启动子上未观察到这种翻译后修饰，我们得出结论，组蛋白H3磷酸化可能是活化的、类维生素A控制的mRARβ2基因启动子的分子特征。
