Phosphoinositide [PI(3,5)P2] lipid-dependent regulation of the general transcriptional regulator Tup1
Phosphoinositide [PI(3,5)P2] lipid-dependent regulation of the general transcriptional regulator Tup1
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DOI：
10.1101/gad.1998611
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发表时间：
2011-05-01
影响因子：
10.5
通讯作者：
Emr, Scott D.
中科院分区：
文献类型：
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作者：
Han, Bong-Kwan;Emr, Scott D.
基因的转录活性受转录调控复合体的控制，这些复合体在基因上组装/拆解，并控制染色质的结构。细胞质成分如何影响转录调控复合体的组装/拆卸，目前还知之甚少。在此，我们报道了出芽酵母的染色质构型调节机制依赖于内体脂质PI(3，5)P-2。我们发现Tup1和Cti6是新的、高度特异的PI(3，5)P-2相互作用因子。Tup1与包括HDAC(组蛋白脱乙酰酶)和SAGA复合体在内的多种转录调节因子相关，在确定包括GAL1在内的许多基因的激活或抑制染色质状态中发挥关键作用。我们发现，在Gal4激活途径受损的情况下，PI(3，5)P-2在将Tup1驱动的抑制的染色质结构转化为GAL1启动子上包含SAGA的激活的染色质结构方面起着至关重要的作用。生化和细胞生物学实验表明，PI(3，5)P-2将Cti6和Cyc8-Tup1辅阻遏子复合体招募到晚期的内体/空泡膜上，并介导Cti6-Cyc8-Tup1共激活复合体的组装，从而将SagA复合体招募到GAL1启动子。我们的发现为理解染色质结构和基因的表观遗传状态是如何由细胞质成分调节的提供了重要的见解。
Transcriptional activity of a gene is governed by transcriptional regulatory complexes that assemble/disassemble on the gene and control the chromatin architecture. How cytoplasmic components influence the assembly/disassembly of transcriptional regulatory complexes is poorly understood. Here we report that the budding yeast Saccharomyces cerevisiae has a chromatin architecture-modulating mechanism that is dependent on the endosomal lipid PI(3,5)P-2. We identified Tup1 and Cti6 as new, highly specific PI(3,5)P-2 interactors. Tup1-which associates with multiple transcriptional regulators, including the HDAC (histone deacetylase) and SAGA complexes-plays a crucial role in determining an activated or repressed chromatin state of numerous genes, including GAL1. We show that, in the context that the Gal4 activation pathway is compromised, PI(3,5)P-2 plays an essential role in converting the Tup1-driven repressed chromatin structure into a SAGA-containing activated chromatin structure at the GAL1 promoter. Biochemical and cell biological experiments suggest that PI(3,5)P-2 recruits Cti6 and the Cyc8-Tup1 corepressor complex to the late endosomal/vacuolar membrane and mediates the assembly of a Cti6-Cyc8-Tup1 coactivator complex that functions to recruit the SAGA complex to the GAL1 promoter. Our findings provide important insights toward understanding how the chromatin architecture and epigenetic status of a gene are regulated by cytoplasmic components.