Combinatorial Histone Acetylation Patterns Are Generated by Motif-Specific Reactions
Combinatorial Histone Acetylation Patterns Are Generated by Motif-Specific Reactions
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DOI：
10.1016/j.cels.2016.01.002
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发表时间：
2016-01-27
期刊：
影响因子：
9.3
通讯作者：
Marr, Carsten
中科院分区：
文献类型：
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作者：
Blasi, Thomas;Feller, Christian;Marr, Carsten
翻译后修饰（PTM）是细胞信息处理的关键，但如何设置组合PTM模式（“基序”）仍然是难以捉摸的。我们开发了一个计算框架，作为开源代码提供，以研究产生果蝇组蛋白H4组合乙酰化模式的设计原则。我们发现假设纯非特异性或赖氨酸位点特异性乙酰化率的模型不足以解释实验确定的基序丰度。相反，这些丰度是最好的描述与特定的基序乙酰化率的模型集合。模型集合集中于四种乙酰化途径；我们使用来自系统酶耗竭研究的独立数据验证了其中的三个。我们的研究结果表明，组蛋白乙酰化模式起源于涉及基序特异性乙酰化活性的特定途径。
Post-translational modifications (PTMs) are pivotal to cellular information processing, but how combinatorial PTM patterns ("motifs'') are set remains elusive. We develop a computational framework, which we provide as open source code, to investigate the design principles generating the combinatorial acetylation patterns on histone H4 in Drosophila melanogaster. We find that models assuming purely unspecific or lysine site-specific acetylation rates were insufficient to explain the experimentally determined motif abundances. Rather, these abundances were best described by an ensemble of models with acetylation rates that were specific to motifs. The model ensemble converged upon four acetylation pathways; we validated three of these using independent data from a systematic enzyme depletion study. Our findings suggest that histone acetylation patterns originate through specific pathways involving motif-specific acetylation activity.