Histone benzoylation serves as an epigenetic mark for DPF and YEATS family proteins.
Histone benzoylation serves as an epigenetic mark for DPF and YEATS family proteins.
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组蛋白苯甲酰化作为 DPF 和 YEATS 家族蛋白的表观遗传标记。
DOI：
10.1093/nar/gkaa1130
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发表时间：
2021-01-11
影响因子：
14.9
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Ren X;Zhou Y;Xue Z;Hao N;Li Y;Guo X;Wang D;Shi X;Li H
组蛋白修饰及其功能读出是基因调控的重要机制。组蛋白上的赖氨酸苯甲酰化（Kbz）是最近发现的与转录活性相关的酰化标记。然而，它仍然有待探讨是否存在假定的读者认识到这一表观遗传标记。在这里，我们的系统结合研究表明，DPF和YEATS，但不是Bromodomain家族成员，是组蛋白Kbz的读者。共晶结构分析揭示了一个“疏水封装”和“尖端传感器”的机制Kbz读出DPF和YEATS，分别。此外，DPF和YEATS家族成员显示出微妙而独特的功能，以创建不同酰化标记的灵活接合。例如，YEATS 2而不是其他YEATS蛋白由于其更宽的“尖端-传感器”口袋而表现出对Kbz比赖氨酸乙酰化和巴豆酰化的最佳偏好。培养细胞或小鼠中组蛋白苯甲酰化的水平在苯甲酸钠处理后上调，突出了其动态调节。总之，我们的工作确定了组蛋白Kbz的第一个读者，并揭示了Kbz识别的分子基础，从而为进一步的功能解剖组蛋白苯甲酰化铺平了道路。
Histone modifications and their functional readout serve as an important mechanism for gene regulation. Lysine benzoylation (Kbz) on histones is a recently identified acylation mark associated with active transcription. However, it remains to be explored whether putative readers exist to recognize this epigenetic mark. Here, our systematic binding studies demonstrated that the DPF and YEATS, but not the Bromodomain family members, are readers for histone Kbz. Co-crystal structural analyses revealed a ‘hydrophobic encapsulation’ and a ‘tip-sensor’ mechanism for Kbz readout by DPF and YEATS, respectively. Moreover, the DPF and YEATS family members display subtle yet unique features to create somewhat flexible engagements of different acylation marks. For instance, YEATS2 but not the other YEATS proteins exhibits best preference for Kbz than lysine acetylation and crotonylation due to its wider ‘tip-sensor’ pocket. The levels of histone benzoylation in cultured cells or in mice are upregulated upon sodium benzoate treatment, highlighting its dynamic regulation. In summary, our work identifies the first readers for histone Kbz and reveals the molecular basis underlying Kbz recognition, thus paving the way for further functional dissections of histone benzoylation.
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影响因子：
5.7
作者：
Flynn, E. Megan;Huang, Oscar W.;Cochran, Andrea G.
通讯作者：
Cochran, Andrea G.
影响因子：
14.9
作者：
Dreveny I;Deeves SE;Fulton J;Yue B;Messmer M;Bhattacharya A;Collins HM;Heery DM
通讯作者：
Heery DM
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
14.8
作者：
Dai, Lunzhi;Peng, Chao;Zhao, Yingming
通讯作者：
Zhao, Yingming
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH