Multi-omic analysis of gametogenesis reveals a novel signature at the promoters and distal enhancers of active genes
Multi-omic analysis of gametogenesis reveals a novel signature at the promoters and distal enhancers of active genes
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DOI：
10.1093/nar/gkaa163
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发表时间：
2020-05-07
影响因子：
14.9
通讯作者：
Pflieger, Delphine
中科院分区：
文献类型：
--
作者：
Crespo, Marion;Damont, Annelaure;Pflieger, Delphine
基因表达的表观遗传调控受到化学基团对组蛋白的动态修饰的严格控制，在过去的十年中，随着酰基辅酶A催化赖氨酸酰化作用的发现，组蛋白的多样性大大增加。我们研究了小鼠精子发生过程中组蛋白H3和H4上赖氨酸乙酰化和巴豆化的动力学。与乙酰化相比，赖氨酸巴豆化似乎具有显著的丰度，特别是在组蛋白H3(H3K27cr)的Lys27上，它以裂解的H3形式积累在精子中。我们鉴定了H3K27cr的基因组定位，并与经典活性标记H3K27ac在启动子和远端增强子上进行了比较，研究了H3K27cr对转录的影响。这两个标记的存在与最高基因表达密切相关。对它们与转录调节因子(Sly，SOX30)和染色质结合蛋白(BRD4，BRDT，Boris和CTCF)的共同定位的评估表明，当两个活性标记都存在时，系统结合最高，而当染色质单独存在时，选择性结合不同。H3K27cr和H3K27ac最终标志着一些精子超级增强剂的建立。与H3K27ac相比，这种组学数据的综合分析提供了对H3K27cr基因表达调控的前所未有的了解，并揭示了每个组蛋白修饰的协同和特定作用。
Epigenetic regulation of gene expression is tightly controlled by the dynamic modification of histones by chemical groups, the diversity of which has largely expanded over the past decade with the discovery of lysine acylations, catalyzed from acyl-coenzymes A. We investigated the dynamics of lysine acetylation and crotonylation on histones H3 and H4 during mouse spermatogenesis. Lysine crotonylation appeared to be of significant abundance compared to acetylation, particularly on Lys27 of histone H3 (H3K27cr) that accumulates in sperm in a cleaved form of H3. We identified the genomic localization of H3K27cr and studied its effects on transcription compared to the classical active mark H3K27ac at promoters and distal enhancers. The presence of both marks was strongly associated with highest gene expression. Assessment of their co-localization with transcription regulators (SLY, SOX30) and chromatin-binding proteins (BRD4, BRDT, BORIS and CTCF) indicated systematic highest binding when both active marks were present and different selective binding when present alone at chromatin. H3K27cr and H3K27ac finally mark the building of some sperm super-enhancers. This integrated analysis of omics data provides an unprecedented level of understanding of gene expression regulation by H3K27cr in comparison to H3K27ac, and reveals both synergistic and specific actions of each histone modification.