Spreading of transcriptional repressor SIR3 from telomeric heterochromatin

Spreading of transcriptional repressor SIR3 from telomeric heterochromatin
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DOI:
10.1038/383092a0
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发表时间:
1996-09-05
期刊:
影响因子:
64.8
通讯作者:
Grunstein, M
Grunstein, M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hecht, A;StrahlBolsinger, S;Grunstein, M

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酿酒酵母的端粒基因和HM位点在转录上受到抑制,并采用异染色质样结构(1,2)。反式作用因子RAP1, SIR3和SIR4是端粒和HM沉默所必需的(3-5),并且被认为是染色体(6-8),但它们如何促进组蛋白依赖性邻近染色质的抑制(9-11)尚不清楚。SIR3抑制组蛋白的沉默缺陷(10),限制端粒附近的沉默(12),并在体外与H3和H4氨基末端相互作用(13)。在这里,我们发现SIR3共同免疫沉淀细胞提取物中的SIR4、RAP1和组蛋白,表明存在大型染色质相关蛋白复合物。交联实验表明SIR3在体内存在于HMRa、HML α和端粒中,当过表达时,SIR3从端粒区域扩散到邻近的染色质中。因此,SIR3是酵母异染色质的一个结构成分,当它沿着染色体扩散时抑制邻近基因。
TELOMERIC genes and the HM loci in Saccharomyces cerevisiae are transcriptionally repressed and adopt a heterochromatin-like structure(1,2). The trans-acting factors RAP1, SIR3 and SIR4 are required for telomeric and HM silencing(3-5): and are thought to be chromosomal(6-8), but how they contribute to histone-dependent repression of adjacent chromatin(9-11) is unclear. SIR3 suppresses silencing defects in histones(10), is limiting for silencing adjacent to telomeres(12), and interacts with the H3 and H4 amino termini in vitro(13), Here we show that SIR3 co-immunoprecipitates SIR4, RAP1 and histones from cellular extracts, suggesting the presence of large chromatin-associated protein complexes. Crosslinking experiments show that SIR3 is present at HMRa, HML alpha and telomeres in vivo, and that it spreads from telomeric regions into adjacent chromatin when overexpressed. Thus SIR3 is a structural component of yeast heterochromatin, repressing adjacent genes as it spreads along the chromosome.