Histone H3K4 and K36 Methylation, Chd1 and Rpd3S Oppose the Functions of Saccharomyces cerevisiae Spt4-Spt5 in Transcription
Histone H3K4 and K36 Methylation, Chd1 and Rpd3S Oppose the Functions of Saccharomyces cerevisiae Spt4-Spt5 in Transcription
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DOI：
10.1534/genetics.109.111526
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发表时间：
2010-02-01
期刊：
影响因子：
3.3
通讯作者：
Hartzog, Grant Ashley
中科院分区：
文献类型：
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作者：
Quan, Tiffani Kiyoko;Hartzog, Grant Ashley
Spt 4-Spt 5是RNA聚合酶II的通用转录延伸因子，也在染色质调节中发挥作用。然而，这些功能之间的关系并不明确。在此之前，我们分离的抑制剂的酿酒酵母spt 5突变的基因编码成员的Paf 1复合物，调节几个共转录组蛋白修饰，和Chd 1，染色质重塑酶。在这里，我们表明，这种抑制spt 5可以导致组蛋白H3赖氨酸4或36甲基化的损失，或减少招募Chd 1或Rpd 3S复合物。这些spt 5抑制子也挽救了在也缺乏延伸因子TFIIS的spt 5突变体中观察到的合成生长缺陷。使用FLO 8报告基因，我们发现，一个chd 1突变引起的隐蔽启动转录。我们进一步观察到在chd 1 isw 1突变体中隐蔽起始的增强和在chd 1突变体中组蛋白乙酰化的增加。我们认为，如先前提出的H3赖氨酸36甲基化和Rpd 3S复合物，H3赖氨酸4甲基化和Chd 1功能，以维持正常的染色质结构转录基因，和Spt 4-Spt 5的功能之一是帮助RNA聚合酶II克服这些组蛋白修饰和染色质调节转录的抑制作用。
Spt4-Spt5, a general transcription elongation factor for RNA polymerase II, also has roles in chromatin regulation. However, the relationships between these functions are not clear. Previously, we isolated suppressors of a Saccharomyces cerevisiae spt5 mutation in genes encoding members of the Paf1 complex, which regulates several cotranscriptional histone modifications, and Chd1, a chromatin remodeling enzyme. Here, we show that this suppression of spt5 can result from loss of histone H3 lysines 4 or 36 methylation, or reduced recruitment of Chd1 or the Rpd3S complex. These spt5 suppressors also rescue the synthetic growth defects observed in spt5 mutants that also lack elongation factor TFIIS. Using a FLO8 reporter gene, we found that a chd1 mutation caused cryptic initiation of transcription. We further observed enhancement of cryptic initiation in chd1 isw1 mutants and increased histone acetylation in a chd1 mutant. We suggest that, as previously proposed for H3 lysine 36 methylation and the Rpd3S complex, H3 lysine 4 methylation and Chd1 function to maintain normal chromatin structures over transcribed genes, and that one function of Spt4-Spt5 is to help RNA polymerase II overcome the repressive effects of these histone modifications and chromatin regulators on transcription.