Silencers, silencing, and heritable transcriptional states.

Silencers, silencing, and heritable transcriptional states.
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沉默子、沉默和可遗传的转录状态。

DOI:
10.1128/mr.56.4.543-560.1992
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发表时间:
1992
期刊:
Microbiological reviews
影响因子:
--
通讯作者:
Rine,J
Rine,J
中科院分区:
--
文献类型:
--
作者:
Laurenson,P;Rine,J

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在芽殖酵母酿酒酵母中发现了决定细胞类型的交配型基因的三个拷贝。MAT基因座上的拷贝是转录活性的,而HML和HMR基因座上的交配型基因的相同拷贝是转录沉默的。因此,HML和HMR,也被称为沉默交配型基因座,受到位置效应的影响。调控序列位于沉默交配型基因座的侧翼,并介导HML和HMR的抑制。这些调控序列被称为沉默子,因为它们能够以不依赖于距离和方向的方式抑制附近基因的转录。此外,许多蛋白质,包括四种SIR蛋白质、组蛋白H4和α-乙酰转移酶,是完全抑制HML和HMR所必需的。由于组蛋白H4氨基末端结构域的改变导致沉默交配型位点的去阻遏,阻遏的机制可能涉及特定染色质结构的组装。一些额外的线索允许洞察HML和HMR抑制的性质。首先,S期事件是建立阻遏所必需的。第二,至少有一个基因似乎在建立机制中发挥作用,但对于通过多轮细胞分裂稳定传播阻遏不是必需的。第三,抑制的某些方面与复制的某些方面有关。沉默交配型基因座与异染色质有许多相似之处。此外,S.已知在其它生物体中异染色质的酿酒酵母染色体,如端粒,需要SIR蛋白的一个子集进行阻遏。进一步分析沉默交配型基因座的转录抑制可能有助于了解其他真核生物中的遗传抑制。
Three copies of the mating-type genes, which determine cell type, are found in the budding yeast Saccharomyces cerevisiae. The copy at the MAT locus is transcriptionally active, whereas identical copies of the mating-type genes at the HML and HMR loci are transcriptionally silent. Hence, HML and HMR, also known as the silent mating-type loci, are subject to a position effect. Regulatory sequences flank the silent mating-type loci and mediate repression of HML and HMR. These regulatory sequences are called silencers for their ability to repress the transcription of nearby genes in a distance- and orientation-independent fashion. In addition, a number of proteins, including the four SIR proteins, histone H4, and an alpha-acetyltransferase, are required for the complete repression of HML and HMR. Because alterations in the amino-terminal domain of histone H4 result in the derepression of the silent mating-type loci, the mechanism of repression may involve the assembly of a specific chromatin structure. A number of additional clues permit insight into the nature of repression at HML and HMR. First, an S phase event is required for the establishment of repression. Second, at least one gene appears to play a role in the establishment mechanism yet is not essential for the stable propagation of repression through many rounds of cell division. Third, certain aspects of repression are linked to aspects of replication. The silent mating-type loci share many similarities with heterochromatin. Furthermore, regions of S. cerevisiae chromosomes, such as telomeres, which are known to be heterochromatic in other organisms, require a subset of SIR proteins for repression. Further analysis of the transcriptional repression at the silent mating-type loci may lend insight into heritable repression in other eukaryotes.
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DOI: 10.1016/s0959-437x(05)80286-2
发表时间: 1992
影响因子: 4
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