The yeast Cyc8-Tup1 complex cooperates with Hda1p and Rpd3p histone deacetylases to robustly repress transcription of the subtelomeric FLO1 gene.
The yeast Cyc8-Tup1 complex cooperates with Hda1p and Rpd3p histone deacetylases to robustly repress transcription of the subtelomeric FLO1 gene.
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DOI：
10.1016/j.bbagrm.2014.07.022
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发表时间：
2014-11
影响因子：
4.7
通讯作者：
Pennings, Sari
中科院分区：
文献类型：
--
作者：
Fleming, Alastair B.;Beggs, Suzanne;Church, Michael;Tsukihashi, Yoshihiro;Pennings, Sari
我们表明，酵母絮凝基因，FLO 1，是一个独特的亚端粒基因的子集，强烈压抑的Cyc 8-Tup 1复合物的代表。我们研究了Cyc 8-Tup 1定位，组蛋白乙酰化和长距离染色质重塑广泛的FLO 1上游区域内。我们发现，Cyc 8-Tup 1定位在一个DNase I超敏位点内的一个有序阵列的强定位的核小体约-700碱基对上游的转录起始位点。在cyc 8缺失突变株，Tup 1 p定位是不存在的，伴随着组蛋白超乙酰化的相邻区域的FLO 1启动子。这伴随着上游区域的广泛组蛋白耗竭和基因激活。酵母组蛋白去乙酰化酶Hda 1 p和Rpd 3 p以Cyc 8-Tup 1依赖的方式占据受抑制的FLO 1启动子区域，并协调组蛋白去乙酰化、核小体稳定和基因抑制。此外，我们发现，ATP依赖的染色质重塑复合物Swi-Snf占据了Cyc 8突变体中Cyc 8-Tup 1空出的位点。这些数据表明，明确结合的Cyc 8-Tup 1与Hda 1 p和Rpd 3 p合作，建立或维持一个广泛的阵列强定位，脱乙酰化的核小体超过FLO 1启动子和上游区域，抑制组蛋白乙酰化，阻止Swi-Snf结合，并防止转录。Cyc 8-Tup 1阻遏活性在染色体亚端粒区域富集。亚端粒FLO 1基因受到Cyc 8-Tup 1的染色质介导的阻遏。Cyc 8-Tup 1促进长距离核小体定位和组蛋白去乙酰化。Hda 1 p和Rpd 3 p与Cyc 8-Tup 1合作以促进这种抑制性染色质。当Cyc 8-Tup 1不存在时，Swi-Snf指导广泛的核小体重塑。
We demonstrate that the yeast flocculation gene, FLO1, is representative of a distinct subset of subtelomeric genes that are robustly repressed by the Cyc8–Tup1 complex. We have examined Cyc8–Tup1 localisation, histone acetylation and long-range chromatin remodelling within the extensive FLO1 upstream region. We show that Cyc8–Tup1 is localised in a DNase I hypersensitive site within an ordered array of strongly positioned nucleosomes around − 700 base pairs upstream of the transcription start site. In cyc8 deletion mutant strains, Tup1p localisation is absent, with concomitant histone hyperacetylation of adjacent regions at the FLO1 promoter. This is accompanied by extensive histone depletion across the upstream region and gene activation. The yeast histone deacetylases, Hda1p and Rpd3p, occupy the repressed FLO1 promoter region in a Cyc8–Tup1 dependent manner and coordinate histone deacetylation, nucleosome stabilisation and gene repression. Moreover, we show that the ATP-dependent chromatin remodelling complex Swi–Snf occupies the site vacated by Cyc8–Tup1 in a cyc8 mutant. These data suggest that distinctly bound Cyc8–Tup1 cooperates with Hda1p and Rpd3p to establish or maintain an extensive array of strongly positioned, deacetylated nucleosomes over the FLO1 promoter and upstream region which inhibit histone acetylation, block Swi–Snf binding and prevent transcription. Cyc8–Tup1 repression activity is enriched at chromosome subtelomeric regions. The subtelomeric FLO1 gene is subject to chromatin-mediated repression by Cyc8–Tup1. Cyc8–Tup1 promotes long-range nucleosome positioning and histone deacetylation. Hda1p and Rpd3p cooperate with Cyc8–Tup1 to facilitate this repressive chromatin. Swi–Snf directs extensive nucleosome remodelling when Cyc8–Tup1 is absent.
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