A novel allele of SIR2 reveals a heritable intermediate state of gene silencing.
A novel allele of SIR2 reveals a heritable intermediate state of gene silencing.
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SIR2 的一个新等位基因揭示了基因沉默的可遗传中间状态。
DOI：
10.1093/genetics/iyab041
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发表时间：
2021
期刊：
影响因子：
3.3
通讯作者：
Rine,Jasper
中科院分区：
文献类型：
--
作者：
Farris,Delaney;Saxton,DanielS;Rine,Jasper
遗传信息通过表观遗传调控获得了额外的意义，在这个过程中，基因相同的细胞可以在基因表达和表型上表现出可遗传的差异。表观遗传信息的遗传是维持细胞身份和机体健康的关键步骤。在酿酒酵母中，表观遗传调控的一种形式是通过 SIR-蛋白复合物对两个交配型基因座 HML 和 HMR 进行转录沉默。为了关注这种基因调控的表观遗传维度，我们进行了正向诱变筛选，以鉴定表现出表观遗传或亚稳态沉默缺陷的突变体。我们利用 HML 和 HMR 的荧光报告基因，筛选酵母菌落的表观遗传沉默缺陷。我们发现了许多独立的 s1 等位基因，这是一种已知稳定表观遗传所需的基因。更有趣的是，我们在 SIR2 内发现了一个错义突变，它编码高度保守的组蛋白脱乙酰酶。与sir1Δ表现出完全沉默或完全表达的状态相比，thissir2等位基因表现出完全沉默或以中间水平表达的可遗传状态。这种独特的沉默缺陷的遗传性质受到 rDNA 拷贝数变化的影响，但并不完全依赖于 rDNA 拷贝数的变化。因此，这项研究揭示了一种可遗传的中间沉默状态，并将这种状态与一个中心沉默因子 Sir2 联系起来。
Genetic information acquires additional meaning through epigenetic regulation, the process by which genetically identical cells can exhibit heritable differences in gene expression and phenotype. Inheritance of epigenetic information is a critical step in maintaining cellular identity and organismal health. InSaccharomyces cerevisiae, one form of epigenetic regulation is the transcriptional silencing of two mating-type loci,HMLandHMR, by the SIR-protein complex. To focus on the epigenetic dimension of this gene regulation, we conducted a forward mutagenesis screen to identify mutants exhibiting an epigenetic or metastable silencing defect. We utilized fluorescent reporters atHMLandHMR, and screened yeast colonies for epigenetic silencing defects. We uncovered numerous independentsir1alleles, a gene known to be required for stable epigenetic inheritance. More interestingly, we recovered a missense mutation withinSIR2, which encodes a highly conserved histone deacetylase. In contrast tosir1Δ, which exhibits states that are either fully silenced or fully expressed, thissir2allele exhibited heritable states that were either fully silenced or expressed at an intermediate level. The heritable nature of this unique silencing defect was influenced by, but not completely dependent on, changes in rDNA copy number. Therefore, this study revealed a heritable state of intermediate silencing and linked this state to a central silencing factor, Sir2.