Shen Chang-Hui, Leblanc Benoit P, Neal Carolyn, Akhavan Ramin, Clark David J
Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-8028, USA.
Mol Cell Biol. 2002 Sep;22(18):6406-16. doi: 10.1128/MCB.22.18.6406-6416.2002.
The relationship between chromatin remodeling and histone acetylation at the yeast CUP1 gene was addressed. CUP1 encodes a metallothionein required for cell growth at high copper concentrations. Induction of CUP1 with copper resulted in targeted acetylation of both H3 and H4 at the CUP1 promoter. Nucleosomes containing upstream activating sequences and sequences farther upstream were the targets for H3 acetylation. Targeted acetylation of H3 and H4 required the transcriptional activator (Ace1p) and the TATA boxes, suggesting that targeted acetylation occurs when TATA-binding protein binds to the TATA box or at a later stage in initiation. We have shown previously that induction results in nucleosome repositioning over the entire CUP1 gene, which requires Ace1p but not the TATA boxes. Therefore, the movement of nucleosomes occurring on CUP1 induction is independent of targeted acetylation. Targeted acetylation of both H3 and H4 also required the product of the SPT10 gene, which encodes a putative histone acetylase implicated in regulation at core promoters. Disruption of SPT10 was lethal at high copper concentrations and correlated with slower induction and reduced maximum levels of CUP1 mRNA. These observations constitute evidence for a novel mechanism of chromatin activation at CUP1, with a major role for the TATA box.
研究了酵母CUP1基因染色质重塑与组蛋白乙酰化之间的关系。CUP1编码一种在高铜浓度下细胞生长所必需的金属硫蛋白。用铜诱导CUP1会导致CUP1启动子处的H3和H4发生靶向乙酰化。含有上游激活序列和更上游序列的核小体是H3乙酰化的靶点。H3和H4的靶向乙酰化需要转录激活因子(Ace1p)和TATA框,这表明当TATA结合蛋白与TATA框结合时或在起始的后期阶段发生靶向乙酰化。我们之前已经表明,诱导会导致整个CUP1基因上的核小体重新定位,这需要Ace1p但不需要TATA框。因此,CUP1诱导时发生的核小体移动独立于靶向乙酰化。H3和H4的靶向乙酰化也需要SPT10基因的产物,该基因编码一种假定的组蛋白乙酰转移酶,参与核心启动子的调控。SPT10的破坏在高铜浓度下是致命的,并且与诱导较慢和CUP1 mRNA的最大水平降低相关。这些观察结果构成了CUP1染色质激活新机制的证据,其中TATA框起主要作用。