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Global Effects on Gene Expression in Fission Yeast by Silencing and RNA Interference Machineries†

机译:沉默和RNA干扰机制对裂殖酵母基因表达的全球影响†

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摘要

Histone modifications influence gene expression in complex ways. The RNA interference (RNAi) machinery can repress transcription by recruiting histone-modifying enzymes to chromatin, although it is not clear whether this is a general mechanism for gene silencing or whether it requires repeated sequences such as long terminal repeats (LTRs). We analyzed the global effects of the Clr3 and Clr6 histone deacetylases, the Clr4 methyltransferase, the zinc finger protein Clr1, and the RNAi proteins Dicer, RdRP, and Argonaute on the transcriptome of Schizosaccharomyces pombe (fission yeast). The clr mutants derepressed similar subsets of genes, many of which also became transcriptionally activated in cells that were exposed to environmental stresses such as nitrogen starvation. Many genes that were repressed by the Clr proteins clustered in extended regions close to the telomeres. Surprisingly few genes were repressed by both the silencing and RNAi machineries, with transcripts from centromeric repeats and Tf2 retrotransposons being notable exceptions. We found no correlation between repression by RNAi and proximity to LTRs, and the wtf family of repeated sequences seems to be repressed by histone deacetylation independent of RNAi. Our data indicate that the RNAi and Clr proteins show only a limited functional overlap and that the Clr proteins play more global roles in gene silencing.
机译:组蛋白修饰以复杂的方式影响基因表达。尽管目前尚不清楚这是否是基因沉默的一般机制,还是是否需要重复序列(例如长末端重复序列(LTR)),但RNA干扰(RNAi)机制可通过募集组蛋白修饰酶至染色质来抑制转录。我们分析了Clr3和Clr6组蛋白脱乙酰基酶,Clr4甲基转移酶,锌指蛋白Clr1和RNAi蛋白Dicer,RdRP和Argonaute对裂殖酵母(裂殖酵母)的转录组的总体影响。 clr突变体可抑制相似的基因子集,其中许多基因在暴露于环境压力(如饥饿)的细胞中也被转录激活。许多受Clr蛋白抑制的基因聚集在靠近端粒的延伸区域。令人惊讶的是,沉默和RNAi机制均抑制了少数基因,着丝粒重复序列和Tf2逆转座子的转录产物是一个明显的例外。我们发现RNAi抑制和接近LTRs之间没有相关性,重复序列的wtf家族似乎被独立于RNAi的组蛋白去乙酰化所抑制。我们的数据表明,RNAi和Clr蛋白仅表现出有限的功能重叠,并且Clr蛋白在基因沉默中起着更广泛的作用。

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