Suppression of intragenic transcription requires the MOT1 and NC2 regulators of TATA-binding protein
Suppression of intragenic transcription requires the MOT1 and NC2 regulators of TATA-binding protein
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DOI：
10.1093/nar/gkt1398
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发表时间：
2014-04-01
影响因子：
14.9
通讯作者：
Timmers, H. Th Marc
中科院分区：
文献类型：
--
作者：
Koster, Maria J. E.;Yildirim, Asli D.;Timmers, H. Th Marc
转录区域的染色质结构构成了基因内转录的屏障。在酵母染色质重塑和Mot 1 p-NC 2调节TATA结合蛋白（TBP）的综合研究中，我们检测到合成的基因内转录抑制的遗传相互作用。在不存在ISW 1重塑因子的情况下，Mot 1 p或NC 2的条件性消耗，但在不存在其他染色质重塑因子的情况下，激活了隐藏的FLO 8启动子。同样，在H3 K36甲基转移酶Set 2 p或Asf 1 p-Rtt 106 p组蛋白H3-H4伴侣（参与维持抑制性染色质环境的重要因素）缺失背景中，Mot 1 p或NC 2的条件性缺失导致基因内FLO 8转录物增加。隐藏的FLO 8启动子的活性与H3水平降低、TBP结合增加和H3 K4的三甲基化相关，并且独立于Spt-Ada-Gcn 5-乙酰转移酶功能。这些数据揭示了TBP的负调控与特异性染色质调节因子的合作，以抑制基因内转录。
Chromatin structure in transcribed regions poses a barrier for intragenic transcription. In a comprehensive study of the yeast chromatin remodelers and the Mot1p-NC2 regulators of TATA-binding protein (TBP), we detected synthetic genetic interactions indicative of suppression of intragenic transcription. Conditional depletion of Mot1p or NC2 in absence of the ISW1 remodeler, but not in the absence of other chromatin remodelers, activated the cryptic FLO8 promoter. Likewise, conditional depletion of Mot1p or NC2 in deletion backgrounds of the H3K36 methyltransferase Set2p or the Asf1p-Rtt106p histone H3-H4 chaperones, important factors involved in maintaining a repressive chromatin environment, resulted in increased intragenic FLO8 transcripts. Activity of the cryptic FLO8 promoter is associated with reduced H3 levels, increased TBP binding and tri-methylation of H3K4 and is independent of Spt-Ada-Gcn5-acetyltransferase function. These data reveal cooperation of negative regulation of TBP with specific chromatin regulators to inhibit intragenic transcription.