Characterization of the plant homeodomain (PHD) reader family for their histone tail interactions
Characterization of the plant homeodomain (PHD) reader family for their histone tail interactions
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DOI：
10.1186/s13072-020-0328-z
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发表时间：
2020-01-24
影响因子：
3.9
通讯作者：
Strahl, Brian D.
中科院分区：
文献类型：
--
作者：
Jain, Kanishk;Fraser, Caroline S.;Strahl, Brian D.
背景植物同源结构域(PHD)指是组蛋白翻译后修饰(PTM)的中央“阅读器”，其含有人类基因组编码的>；100个PHD指蛋白。到目前为止，许多被研究的博士结合到组蛋白H3赖氨酸4(H3K4)的未修饰或甲基化状态。此外，这些结构域中的许多以及它们所包含的蛋白质在基因表达和癌症发展的调节中起着至关重要的作用。尽管如此，大多数博士的手指都没有特征化；因此，我们对这些区域如何对染色质生物学做出贡献的理解仍然不完整。结果我们利用阅读器结构域微阵列表达并筛选了123个带注释的人类PHD手指的组蛋白结合偏好。这些结构域的一个子集(31)显示出对H3N-末端尾部的强烈偏好，无论是未修饰的还是在H3K4上甲基化的。用组蛋白多肽芯片和/或AlphaScreen进一步表征这些H3阅读器，以全面确定他们的H3偏好和PTM串扰。结论本研究中使用的高通量方法建立了关于PHD阅读器家族如何与组蛋白PTM结合的结合信息概要，并揭示了几个新的阅读器结构域-组蛋白PTM相互作用(即PHRF1和TRIM66)。这项研究强调了高通量分析组蛋白阅读器蛋白的有用性，作为一种了解染色质参与如何发生的生化手段。
Background Plant homeodomain (PHD) fingers are central "readers" of histone post-translational modifications (PTMs) with > 100 PHD finger-containing proteins encoded by the human genome. Many of the PHDs studied to date bind to unmodified or methylated states of histone H3 lysine 4 (H3K4). Additionally, many of these domains, and the proteins they are contained in, have crucial roles in the regulation of gene expression and cancer development. Despite this, the majority of PHD fingers have gone uncharacterized; thus, our understanding of how these domains contribute to chromatin biology remains incomplete. Results We expressed and screened 123 of the annotated human PHD fingers for their histone binding preferences using reader domain microarrays. A subset (31) of these domains showed strong preference for the H3 N-terminal tail either unmodified or methylated at H3K4. These H3 readers were further characterized by histone peptide microarrays and/or AlphaScreen to comprehensively define their H3 preferences and PTM cross-talk. Conclusions The high-throughput approaches utilized in this study establish a compendium of binding information for the PHD reader family with regard to how they engage histone PTMs and uncover several novel reader domain-histone PTM interactions (i.e., PHRF1 and TRIM66). This study highlights the usefulness of high-throughput analyses of histone reader proteins as a means of understanding how chromatin engagement occurs biochemically.