Role of histone modifications and early termination in pervasive transcription and antisense-mediated gene silencing in yeast
Role of histone modifications and early termination in pervasive transcription and antisense-mediated gene silencing in yeast
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DOI：
10.1093/nar/gku100
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发表时间：
2014-04-01
影响因子：
14.9
通讯作者：
Stutz, Francoise
中科院分区：
文献类型：
--
作者：
Castelnuovo, Manuele;Zaugg, Judith B.;Stutz, Francoise
大多数基因组，包括酵母酿酒酵母，普遍转录产生许多非编码RNA，其中许多是不稳定的，并通过细胞核或细胞质监视途径消除。我们先前表明，在缺乏核外泌体组分Rrp 6的细胞中，PHO 84反义RNA（asRNA）的积累通过在依赖于Hda 1组蛋白脱乙酰酶（HDAC）和H3 K4组蛋白甲基转移酶Set 1的过程中抑制有义转录来抑制。在这里，我们调查这一过程的全基因组和测量的各种组蛋白修饰突变体在三角洲rrp 6株使用平铺阵列的整个转录组。我们证实广泛发生的潜在反义依赖性基因调控，并确定三个功能不同的类的基因积累asRNA的Rrp 6的情况下。这些类别的差异在于基因是否被asRNA沉默，以及沉默是否是HDAC和组蛋白甲基转移酶依赖性的。在具有调控潜力的asRNA的显著特征中，我们鉴定了Nrd 1/Nab 3/Sen 1的弱早期终止，asRNA延伸到开放阅读框启动子中，以及沉默能力对Set 1和HDACs Hda 1和Rpd 3的依赖性，特别是在经历广泛染色质重塑的启动子处。最后，根据Nrd 1/Nab 3/Sen 1早期终止的效率，asRNA水平被调节，并且它们的沉默能力被改变。
Most genomes, including yeast Saccharomyces cerevisiae, are pervasively transcribed producing numerous non-coding RNAs, many of which are unstable and eliminated by nuclear or cytoplasmic surveillance pathways. We previously showed that accumulation of PHO84 antisense RNA (asRNA), in cells lacking the nuclear exosome component Rrp6, is paralleled by repression of sense transcription in a process dependent on the Hda1 histone deacetylase (HDAC) and the H3K4 histone methyl transferase Set1. Here we investigate this process genome-wide and measure the whole transcriptome of various histone modification mutants in a Delta rrp6 strain using tiling arrays. We confirm widespread occurrence of potentially antisense-dependent gene regulation and identify three functionally distinct classes of genes that accumulate asRNAs in the absence of Rrp6. These classes differ in whether the genes are silenced by the asRNA and whether the silencing is HDACs and histone methyl transferase-dependent. Among the distinguishing features of asRNAs with regulatory potential, we identify weak early termination by Nrd1/Nab3/Sen1, extension of the asRNA into the open reading frame promoter and dependence of the silencing capacity on Set1 and the HDACs Hda1 and Rpd3 particularly at promoters undergoing extensive chromatin remodelling. Finally, depending on the efficiency of Nrd1/Nab3/Sen1 early termination, asRNA levels are modulated and their capability of silencing is changed.