School of Life Sciences; Södertörn University, Huddinge, Sweden.
Cell Cycle. 2010 Feb 1;9(3):467-71. doi: 10.4161/cc.9.3.10543.
We previously reported genome-wide evidence that the Gcn5 histone acetyltransferase (HAT) is located in the transcribed region of highly expressed genes and that it plays an important role in transcriptional elongation in the fission yeast, Schizosaccharomyces pombe (EMBO Reports 2009; 10:1009-14). Furthermore, the specific interplay between Gcn5 and the Clr3 histone deacetylase (HDAC) controls the acetylation levels of lysine-14 in histone H3 in the same class of highly expressed genes. Mutants of histone H3 that cannot be acetylated at residue 14 show similar stress phenotypes to those observed for mutants lacking Gcn5. In this Extra View article we review these findings in relation to related literature and extend important aspects of the original study. Notably, Gcn5 and Gcn5-dependent acetylation of histone H3K14 tend to be more enriched in the upstream regions of genes that require Gcn5 for correct expression compared to genes that are independent of Gcn5. This suggests a critical role of Gcn5 in the transcriptional initiation of these genes. Gcn5 is however most highly enriched in the transcribed regions of these gene sets but there is no difference between Gcn5-dependent and Gcn5-independent gene sets. Thus we suggest that Gcn5 plays an important but redundant role in the transcriptional elongation of these genes. The Sir2 HDAC has a similar genomic localization and enzymatic activity to Clr3. We studied gcn5Deltasir2Delta double mutants that do not show a suppressed phenotype in relation to gcn5Delta single mutants, compared to gcn5Deltaclr3Delta mutants that do, in order to better understand the specificity of the interplay between Gcn5 and Clr3. In some classes of non-highly expressed genes the clr3Delta mutant tends to restore levels of histone H3K14 acetylation in the double mutant strain more effectively than sir2Delta.
我们之前报道了全基因组证据，表明 Gcn5 组蛋白乙酰转移酶（HAT）位于高度表达基因的转录区域，并且在裂殖酵母 Schizosaccharomyces pombe 中发挥重要作用，参与转录延伸（EMBO Reports 2009；10:1009-14）。此外，Gcn5 和 Clr3 组蛋白去乙酰化酶（HDAC）之间的特定相互作用控制同一类高度表达基因中组蛋白 H3 赖氨酸 14 的乙酰化水平。不能在残基 14 处乙酰化的组蛋白 H3 突变体显示出与缺乏 Gcn5 的突变体相似的应激表型。在这篇额外视图文章中，我们回顾了这些发现与相关文献的关系，并扩展了原始研究的重要方面。值得注意的是，与 Gcn5 不依赖的基因相比，Gcn5 和 Gcn5 依赖性的组蛋白 H3K14 乙酰化在需要 Gcn5 正确表达的基因的上游区域更为丰富。这表明 Gcn5 在这些基因的转录起始中起着关键作用。然而，Gcn5 在这些基因集的转录区域中最为丰富，但 Gcn5 依赖性和 Gcn5 非依赖性基因集之间没有差异。因此，我们认为 Gcn5 在这些基因的转录延伸中发挥重要但冗余的作用。Sir2 HDAC 具有与 Clr3 相似的基因组定位和酶活性。我们研究了 gcn5Deltasir2Delta 双突变体，与 gcn5Deltaclr3Delta 突变体相比，gcn5Deltasir2Delta 双突变体在 gcn5Delta 单突变体中没有表现出抑制表型，以更好地理解 Gcn5 和 Clr3 之间相互作用的特异性。在一些非高度表达基因的类群中，clr3Delta 突变体在双突变体菌株中更有效地恢复组蛋白 H3K14 乙酰化水平，而 sir2Delta 则不然。
