Combinatorial effects of four histone modifications in transcription and differentiation
Combinatorial effects of four histone modifications in transcription and differentiation
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DOI：
10.1016/j.ygeno.2007.08.010
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发表时间：
2008-01-01
期刊：
影响因子：
4.4
通讯作者：
Sperling, Silke
中科院分区：
文献类型：
--
作者：
Fischer, Jenny J.;Toedling, Joern;Sperling, Silke
核小体参与DNA压缩和转录调控。然而，目前尚不清楚组蛋白修饰标记是主要的还是次要的转录，以及它们是否相互作用形成组蛋白密码。我们使用ChIP-chip芯片和表达芯片研究了转录与四种历史性修饰（H4ac, H3ac, H3K4me2/3）之间的关系，这些修饰来自两个小鼠细胞系，一个处于两个分化阶段。我们发现它们与转录水平的关联很大程度上取决于组蛋白修饰的组合。H3K4me2仅与乙酰化结合时表达水平升高，而Mac阳性关联因共同发生的修饰而减弱。在分化过程中，上调的转录本经常获得H4ac，而大多数修饰转换与表达变化无关。我们的研究结果表明，组蛋白修饰形成了一个密码，因为它们的组合组成与不同的读数有关。历史可能主要作为特定效应器的信号标记，而不是转录的充分驱动力或结果。(C) 2007爱思唯尔公司版权所有。
Nucleosomes are involved in DNA compaction and transcriptional regulation. Yet it is unclear whether histone modification marks are primary or secondary to transcription and whether they interact to form a histone code. We investigated the relationship between transcription and four historic modifications (H4ac, H3ac, H3K4me2/3) using ChIP-chip and expression microarray readouts from two murine cell lines, one in two differentiation stages. We found that their association with transcript levels strongly depends on the combination of histone modifications. H3K4me2 coincides with elevated expression levels only in combination with acetylation, while Mac positive association is diminished by co-occurring modifications. During differentiation, upregulated transcripts frequently gain H4ac, while most modification conversions are uncorrelated with expression changes. Our results suggest histone modifications form a code, as their combinatorial composition is associated with distinct readouts. Histories may primarily function as signaling marks for specific effectors rather than being a sufficient driving force for or a consequence of transcription. (C) 2007 Elsevier Inc. All rights reserved.