Imoberdorf Rachel Maria, Topalidou Irini, Strubin Michel
Department of Microbiology and Molecular Medicine, University Medical Centre (C.M.U.), Rue Michel-Servet 1, 1211 Geneva 4, Switzerland.
Mol Cell Biol. 2006 Mar;26(5):1610-6. doi: 10.1128/MCB.26.5.1610-1616.2006.
Transcriptional activators often require histone acetyltransferases (HATs) for full activity. The common explanation is that activators directly recruit HATs to gene promoters to locally hyperacetylate histones and thereby facilitate transcription complex formation. However, in addition to being targeted to specific loci, HATs such as Gcn5 also modify histones genome-wide. Here we provide evidence for a role of this global HAT activity in regulated transcription. We show that activation by direct recruitment of the transcriptional machinery neither recruits Gcn5 nor induces changes in histone acetylation yet can strongly depend on Gcn5 at promoters showing a high basal state of Gcn5-mediated histone acetylation. We also show that Gcn5 dependency varies among core promoters and is influenced by the strength of interaction used to recruit the machinery and by the affinity of the latter for the core promoter. These data support a role for global Gcn5 HAT activity in modulating transcription independently of its known coactivator function.
转录激活因子通常需要组蛋白乙酰转移酶（HATs）才能发挥全部活性。常见的解释是，激活因子直接将HATs招募到基因启动子上，使组蛋白在局部发生高度乙酰化，从而促进转录复合物的形成。然而，除了靶向特定基因座外，诸如Gcn5等HATs还会在全基因组范围内修饰组蛋白。在此，我们提供了这种全局性HAT活性在调控转录中作用的证据。我们表明，通过直接招募转录机制进行的激活既不会招募Gcn5，也不会诱导组蛋白乙酰化的变化，但在显示出Gcn5介导的组蛋白乙酰化高基础状态的启动子处，其强烈依赖于Gcn5。我们还表明，Gcn5的依赖性在核心启动子之间存在差异，并受到用于招募转录机制的相互作用强度以及后者对核心启动子亲和力的影响。这些数据支持全局性Gcn5 HAT活性在独立于其已知的共激活因子功能来调节转录中发挥作用。
