Gregory P D, Schmid A, Zavari M, Lui L, Berger S L, Hörz W
Institut für Physiologische Chemie, Universität München, Germany.
Mol Cell. 1998 Mar;1(4):495-505. doi: 10.1016/s1097-2765(00)80050-7.
Histone acetyltransferase (HAT) activity has been demonstrated for several transcriptional activators, formally connecting chromatin modification with gene regulation. However, no effect on chromatin has been demonstrated. We have investigated the role of the HAT Gcn5 at the nucleosomally regulated PHO5 promoter. Under conditions of constitutive submaximal activation (i.e., in the absence of the negative regulator Pho80), deletion of Gcn5 determines a novel randomized nucleosomal organization across the promoter and leads to a dramatic reduction in activity. Furthermore, mutation of amino acids critical for Gcn5 HAT activity is sufficient to generate this structure. This intermediate state in chromatin opening gives way to the fully open structure upon maximal induction (phosphate starvation), even in the absence of Gcn5. Thus, Gcn5 is shown to affect directly the remodeling of chromatin in vivo.
已证实几种转录激活因子具有组蛋白乙酰转移酶（HAT）活性，从而正式将染色质修饰与基因调控联系起来。然而，尚未证实其对染色质有影响。我们研究了HAT Gcn5在核小体调节的PHO5启动子中的作用。在组成型亚最大激活条件下（即在没有负调节因子Pho80的情况下），Gcn5的缺失决定了启动子上新的随机核小体组织，并导致活性显著降低。此外，对Gcn5 HAT活性至关重要的氨基酸突变足以产生这种结构。染色质开放的这种中间状态在最大诱导（磷酸盐饥饿）时会转变为完全开放的结构，即使没有Gcn5也是如此。因此，Gcn5被证明在体内直接影响染色质重塑。
