Selective recognition of histone crotonylation by double PHD fingers of MOZ and DPF2.
Selective recognition of histone crotonylation by double PHD fingers of MOZ and DPF2.
复制标题
通过MOZ和DPF2的双PHD手指对组蛋白共同识别的选择性识别。
DOI：
10.1038/nchembio.2218
复制
发表时间：
2016-12
影响因子：
14.8
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Xiong X;Panchenko T;Yang S;Zhao S;Yan P;Zhang W;Xie W;Li Y;Zhao Y;Allis CD;Li H
“阅读器”模块识别组蛋白共价修饰构成了表观遗传调控的主要机制。最近新发现的组蛋白赖氨酸酰化反应，如巴豆化(KCR)、丁酰化(KBU)和丙酰化(KPR)，极大地扩展了组蛋白赖氨酸修饰的编码潜力。在这里，我们证明了组蛋白乙酰化结合的双PHD指(DPF)结构域的人MoZ(又名。KAT6A)和DPF2(又名BAF45d)适应了广泛的组蛋白赖氨酸酰化反应，其中对KCR的偏好最强。MoZ的DPF结构域与H3K14cr、H3K14bu和H3K14Pr多肽形成的络合物的晶体结构表明，这些非乙酰酰化作用锚定在一个疏水的“死端”口袋中，通过紧密的封装和酰胺敏感的氢键网络来选择性地进行巴豆化反应。免疫荧光和芯片定量聚合酶链式反应显示，MoZ和H3K14cr以DPF依赖的方式共定位。我们的研究提醒人们注意一种新的调控机制，该机制以DPF家族成员读出的组蛋白巴豆化为中心。
Recognition of histone covalent modifications by “reader” modules constitutes a major mechanism for epigenetic regulation. A recent upsurge of newly discovered histone lysine acylations, such as crotonylation (Kcr), butyrylation (Kbu), and propionylation (Kpr), greatly expands the coding potential of histone lysine modifications. Here we demonstrate that the histone acetylation-binding double PHD finger (DPF) domains of human MOZ (a.k.a. KAT6A) and DPF2 (a.k.a. BAF45d) accommodate a wide range of histone lysine acylations with the strongest preference for Kcr. Crystal structures of the DPF domain of MOZ in complex with H3K14cr, H3K14bu, and H3K14pr peptides reveal that these non-acetyl acylations are anchored in a hydrophobic “dead-end” pocket with selectivity for crotonylation arising from intimate encapsulation and amide-sensing hydrogen bonding network. Immunofluorescence and ChIP-qPCR show that MOZ and H3K14cr colocalize in a DPF-dependent manner. Our studies call attention to a new regulatory mechanism centered on histone crotonylation readout by DPF family members.