HistoneHits: A database for histone mutations and their phenotypes
HistoneHits: A database for histone mutations and their phenotypes
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DOI：
10.1101/gr.083402.108
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发表时间：
2009-04-01
期刊：
影响因子：
7
通讯作者：
Bader, Joel S.
中科院分区：
文献类型：
--
作者：
Huang, Hailiang;Maertens, Alexandra M.;Bader, Joel S.
组蛋白是核小体的基本蛋白质组分。它们是最保守的蛋白质之一，并且受到过多的翻译后修饰。特定的组蛋白残基在建立染色质结构、调节基因表达和沉默以及响应DNA损伤中是重要的。在这里，我们提出HistoneHits，一个表型数据库，用于系统收集组蛋白突变体。该数据库将分析结果（表型）与有关序列、结构、翻译后修饰和进化保守性的信息相结合。网络界面通过动态表格和图形呈现信息。它计算特定突变体和核小体表面数据的可用性。该数据库目前包括对677种突变体的42种测定，这些突变体复盖了酵母组蛋白H3、H4、H2A和H2B中498个残基中的405个。我们还提供了一个接口，可扩展的控制词汇表的研究小组提交新的数据。初步分析证实，在高度保守的残基和可修饰的残基的突变更有可能产生表型。掩埋残基和侧表面残基倾向于产生更多的表型，而尾部残基产生的表型比其他残基显著更少。酵母突变体与已知的人类组蛋白变体交叉参考，鉴定酵母突变体导致核糖体沉默丧失和人类变体增加乳腺癌易感性的位置。所有数据集均可免费下载。
Histones are the basic protein components of nucleosomes. They are among the most conserved proteins and are subject to a plethora of post-translational modifications. Specific histone residues are important in establishing chromatin structure, regulating gene expression and silencing, and responding to DNA damage. Here we present HistoneHits, a database of phenotypes for systematic collections of histone mutants. This database combines assay results (phenotypes) with information about sequences, structures, post-translational modifications, and evolutionary conservation. The web interface presents the information through dynamic tables and figures. It calculates the availability of data for specific mutants and for nucleosome surfaces. The database currently includes 42 assays on 677 mutants multiply covering 405 of the 498 residues across yeast histones H3, H4, H2A, and H2B. We also provide an interface with an extensible controlled vocabulary for research groups to submit new data. Preliminary analyses confirm that mutations at highly conserved residues and modifiable residues are more likely to generate phenotypes. Buried residues and residues on the lateral surface tend to generate more phenotypes, while tail residues generate significantly fewer phenotypes than other residues. Yeast mutants are cross referenced with known human histone variants, identifying a position where a yeast mutant causes loss of ribosomal silencing and a human variant increases breast cancer susceptibility. All data sets are freely available for download.