Kanno Tomohiko, Kanno Yuka, Siegel Richard M, Jang Moon Kyoo, Lenardo Michael J, Ozato Keiko
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Mol Cell. 2004 Jan 16;13(1):33-43. doi: 10.1016/s1097-2765(03)00482-9.
Acetylation and other modifications on histones 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 histones 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 bromodomains. 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 bromodomains is selective, is involved in transcription, and potentially conveys transcriptional memory across cell divisions.
组蛋白上的乙酰化及其他修饰构成了调控染色质转录调控过程的组蛋白密码。然而，对于不同的组蛋白密码如何被解读并发挥作用，我们却知之甚少。利用荧光共振能量转移技术，我们发现含溴结构域的蛋白质能够在活细胞的完整细胞核中识别不同模式的乙酰化组蛋白。含溴结构域蛋白Brd2能选择性地与组蛋白H4上乙酰化的赖氨酸12相互作用，而TAF(II)250和PCAF则识别H3及其他乙酰化组蛋白，这表明不同的溴结构域对组蛋白的识别具有精细的特异性。这种相互作用的层级关系在直接肽结合实验中也能观察到。与乙酰化组蛋白的相互作用对Brd2增强转录至关重要。此外，在有丝分裂期间，Brd2而非其他含溴结构域蛋白与乙酰化染色质的结合会持续存在于染色体上。因此，溴结构域对组蛋白乙酰化密码的识别具有选择性，参与转录过程，并可能在细胞分裂过程中传递转录记忆。
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