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The SAGA Subunit Ada2 Functions in Transcriptional Silencing

机译:SAGA亚基Ada2在转录沉默中的功能

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The cellular role of the Ada2 coactivator is currently understood in the context of the SAGA histone acetyltransferase (HAT) complex, where Ada2 increases the HAT activity of Gcn5 and interacts with transcriptional activators. Here we report a new function for Ada2 in promoting transcriptional silencing at telomeres and ribosomal DNA. This silencing function is the first characterized role for Ada2 distinct from its involvement with Gcn5. Ada2 binds telomeric chromatin and the silencing protein Sir2 in vivo. Loss of ADA2 causes the spreading of Sir2 and Sir3 into subtelomeric regions and decreased histone H4 K16 acetylation. This previously uncharacterized boundary activity of Ada2 is functionally similar to, but mechanistically distinct from, that of the MYST family HAT Sas2. Mounting evidence in the literature indicates that boundary activities create chromosomal domains important for regulating gene expression in response to environmental changes. Consistent with this, we show that upon nutritional changes, Ada2 occupancy increases at a subtelomeric region proximal to a SAGA-inducible gene and causes derepression of a silenced telomeric reporter gene. Thus, Ada2, likely in the context of SAGA, is positioned at chromosomal termini to participate in both transcriptional repression and activation in response to nutrient signaling.
机译:目前,在SAGA组蛋白乙酰转移酶(HAT)复合物的背景下理解了Ada2共激活剂的细胞作用,其中Ada2增加了Gcn5的HAT活性并与转录激活剂相互作用。在这里,我们报告Ada2在促进端粒和核糖体DNA转录沉默方面的新功能。该沉默功能是Ada2的第一个特征性角色,与它与Gcn5的参与不同。 Ada2在体内结合端粒染色质和沉默蛋白Sir2。 ADA2 的缺失会导致Sir2和Sir3扩散到亚端粒区域,并降低组蛋白H4 K16乙酰化。 Ada2以前未知的边界活性在功能上与MYST家族HAT Sas2相似,但在机械上却与之不同。文献中越来越多的证据表明边界活动产生了染色体结构域,该结构域对于响应环境变化调节基因表达很重要。与此相符,我们表明营养改变后,Ada2占有率在SAGA可诱导基因附近的亚端粒区域增加,并导致沉默端粒报道基因的抑制。因此,可能在SAGA环境中将Ada2定位在染色体末端,以响应营养信号传导而参与转录抑制和激活。

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