Selective recognition of acetylated histones by bromodomain proteins visualized in living cells
Selective recognition of acetylated histones by bromodomain proteins visualized in living cells
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DOI：
10.1016/s1097-2765(03)00482-9
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发表时间：
2004-01-16
期刊：
影响因子：
16
通讯作者：
Ozato, K
中科院分区：
文献类型：
--
作者：
Kanno, T;Kanno, Y;Ozato, K
乙酰化和其他历史上的修改包括组蛋白编码，控制在染色质中的转录调控过程。然而，人们对不同的组蛋白密码是如何被翻译并发挥作用的知之甚少。使用荧光共振能量转移，我们表明，含溴结构域的蛋白质识别不同模式的乙酰化的历史在完整的活细胞核。溴结构域蛋白Brd2选择性地与组蛋白H4上的乙酰化赖氨酸12相互作用，而TAF（II）250和PCAF识别H3和其他乙酰化组蛋白，表明不同溴结构域对组蛋白识别具有良好的特异性。在直接肽结合测定中也观察到这种相互作用层次。与乙酰化组蛋白的相互作用是必不可少的Brd2扩增转录。此外，协会的Brd2，而不是其他溴结构域蛋白，与乙酰化染色质在有丝分裂过程中染色体上持续。因此，组蛋白乙酰化密码被溴化蛋白识别是选择性的，参与转录，并可能在细胞分裂中传递转录记忆。
Acetylation and other modifications on histories comprise histone codes that govern transcriptional regulatory processes in chromatin. Yet little is known how different histone codes are translated and put into action. Using fluorescence resonance energy transfer, we show that bromodomain-containing proteins recognize different patterns of acetylated histories in intact nuclei of living cells. The bromodomain protein Brd2 selectively interacted with acetylated lysine 12 on histone H4, whereas TAF(II)250 and PCAF recognized H3 and other acetylated histones, indicating fine specificity of histone recognition by different bromodo-mains. This hierarchy of interactions was also seen in direct peptide binding assays. Interaction with acetylated histone was essential for Brd2 to amplify transcription. Moreover association of Brd2, but not other bromodomain proteins, with acetylated chromatin persisted on chromosomes during mitosis. Thus the recognition of histone acetylation code by bromodo-mains is selective, is involved in transcription, and potentially conveys transcriptional memory across cell divisions.