GCN5-dependent histone H3 acetylation and RPD3-dependent histone H4 deacetylation have distinct, opposing effects on IME2 transcription, during meiosis and during vegetative growth, in budding yeast
GCN5-dependent histone H3 acetylation and RPD3-dependent histone H4 deacetylation have distinct, opposing effects on IME2 transcription, during meiosis and during vegetative growth, in budding yeast
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DOI：
10.1073/pnas.96.12.6835
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发表时间：
1999-06-08
影响因子：
11.1
通讯作者：
Kleckner, N
中科院分区：
文献类型：
--
作者：
Burgess, SM;Ajimura, M;Kleckner, N
二倍体酵母在某些营养限制条件下经历减数分裂，这会引发转录级联反应，涉及两个关键的调节基因。 IME1是IME2的阳性激活因子，它激活下游基因。我们报告说，一种组蛋白H3乙酰酶GCN5通过对IME2表达的影响在减数分裂中起着核心作用。等位基因GCN5-21被分离为孢子形成中的突变体有缺陷。 GCN5-21未能进行减数分裂DNA复制，重组或减数分裂分裂。该突变体也无法诱导IME2转录。但是，IME1转录基本上是正常的。进一步的研究表明，在野生型减数分裂过程中，IME2启动子经历了结合的乙酰化组蛋白H3水平的增加，这种增加与IME2转录的减数分裂诱导同时增加，相反，GCN5-21中没有RPD3基因，RPD3基因是RPD3基因编码组蛋白H4脱乙酰基酶，已知是抑制生长酵母中基底IME2转录所必需的细胞不参与减数分裂过程中IME2转录或IME2组蛋白乙酰化的诱导，这些和其他结果表明GCN5和RPD3起着不同的作用，在两个不同的细胞条件下在相反的方向上调节转录启动。这些作用是通过两个基因产物对两个不同组蛋白的乙酰化的相反作用来实现的，最后，我们发现如果不存在乙酸盐，gcn5和rpd3单突变体在减数分裂中不会有缺陷，并且由代谢不相关的碳源促进呼吸。可能通过控制组蛋白乙酰化模式来调节减数分裂。
Diploid yeast undergo meiosis under certain conditions of nutrient limitation, which trigger a transcriptional cascade involving two key regulatory genes. IME1 is a positive activator of IME2, which activates downstream genes. We report that Gcn5, a histone H3 acetylase, plays a central role in initiation of meiosis via effects on IME2 expression. An allele, gcn5-21, was isolated as a mutant defective in spore formation. gcn5-21 fails to carry out meiotic DNA replication, recombination, or meiotic divisions. This mutant also fails to induce IME2 transcription; IME1 transcription, however, is essentially normal. Further investigation shows that during wild-type meiosis the IME2 promoter undergoes an increase in the level of bound acetylated histone H3, This increase is contemporaneous with meiotic induction of IME2 transcription and is absent in gcn5-21, In contrast, the RPD3 gene, which encodes a histone H4 deacetylase and is known to be required for repression of basal IME2 transcription in growing yeast cells, is not involved in induction of IME2 transcription or IME2 histone acetlyation during meiosis, These and other results suggest that Gcn5 and Rpd3 play distinct roles, modulating transcription initiation in opposite directions under two different cellular conditions. These roles are implemented via opposing effects of the two gene products on acetylation of two different histones, Finally, we find that gcn5 and rpd3 single mutants are not defective in meiosis if acetate is absent and respiration is promoted by a metabolically unrelated carbon source. Perhaps intracellular acetate levels regulate meiosis by controlling histone acetylation patterns.