Reid Juliet L, Moqtaderi Zarmik, Struhl Kevin
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Mol Cell Biol. 2004 Jan;24(2):757-64. doi: 10.1128/MCB.24.2.757-764.2004.
Saccharomyces cerevisiae has a global pattern of histone acetylation in which histone H3 and H4 acetylation levels are lower at protein-coding sequences than at promoter regions. The loss of Eaf3, a subunit of the NuA4 histone acetylase and Rpd3 histone deacetylase complexes, greatly alters the genomic profile of histone acetylation, with the effects on H4 appearing to be more pronounced than those on H3. Specifically, the loss of Eaf3 causes increases in H3 and H4 acetylation at coding sequences and decreases at promoters, such that histone acetylation levels become evenly distributed across the genome. Eaf3 does not affect the overall level of H4 acetylation, the recruitment of the NuA4 catalytic subunit Esa1 to target promoters, or the level of transcription of the genes analyzed for histone acetylation. Whole-genome transcriptional profiling indicates that Eaf3 plays a positive, but quantitatively modest, role in the transcription of a small subset of genes, whereas it has a negative effect on very few genes. We suggest that Eaf3 regulates the genomic profile of histone H3 and H4 acetylation in a manner that does not involve targeted recruitment and is independent of transcriptional activity.
酿酒酵母具有一种全局的组蛋白乙酰化模式,其中在蛋白质编码序列处组蛋白H3和H4的乙酰化水平低于启动子区域。NuA4组蛋白乙酰转移酶和Rpd3组蛋白去乙酰化酶复合物的一个亚基Eaf3的缺失,极大地改变了组蛋白乙酰化的基因组图谱,对H4的影响似乎比对H3的影响更明显。具体而言,Eaf3的缺失导致编码序列处H3和H4的乙酰化增加,启动子处的乙酰化减少,从而使组蛋白乙酰化水平在整个基因组中均匀分布。Eaf3不影响H4乙酰化的总体水平、NuA4催化亚基Esa1向目标启动子的募集,也不影响用于分析组蛋白乙酰化的基因的转录水平。全基因组转录谱分析表明,Eaf3在一小部分基因的转录中起积极但数量上适度的作用,而对极少数基因有负面影响。我们认为,Eaf3以一种不涉及靶向募集且独立于转录活性的方式调节组蛋白H3和H4乙酰化的基因组图谱。