Combinatorial Histone H3 Modifications Are Dynamically Altered in Distinct Cell Cycle Phases.
Combinatorial Histone H3 Modifications Are Dynamically Altered in Distinct Cell Cycle Phases.
复制标题
组合组蛋白H3修饰在不同的细胞周期阶段动态改变。
DOI：
10.1021/jasms.0c00451
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发表时间：
2021-06-02
影响因子：
3.2
通讯作者：
Garcia BA
中科院分区：
文献类型：
--
作者：
Lu C;Coradin M;Janssen KA;Sidoli S;Garcia BA
细胞周期是一个高度调节和进化保守的过程，导致细胞内容物的复制和复制的染色体均匀分布到一对子细胞中。组蛋白是真核细胞染色质的基本结构成分，其翻译后修饰（PTM）是DNA读出和染色体浓缩的基准。与组蛋白PTM的失调相关的细胞周期的异常调节是诸如癌症的危重疾病的原因。监测组蛋白PTM的变化可以为理解与细胞增殖的表观遗传调控相关的分子机制铺平道路。以前，我们的实验室建立了一种新的中间向下的工作流程，使用多孔石墨碳（PGC）作为固定相来分析组蛋白PTM，其利用与经典蛋白质组学结合在线MS相同的反相色谱进行梯度分离。在这里，我们将这种新的工作流程应用于细胞周期期间H3.1和H3.2组蛋白修饰的高通量分析。总的来说，我们确定了1133个独特的修改典型的组蛋白H3 N-末端尾巴。与以前的研究结果一致，组蛋白H3磷酸化在M期显著增加。观察到PTM的组蛋白H3变体特异性和细胞周期依赖性表达，强调了不将联合收割机H3.1和H3.2组合在一起作为H3的需要。我们证实了以前已知的H3 PTM串扰（例如K9 me-S10 ph），并揭示了该领域的新信息。这些发现意味着组合PTM在细胞周期控制中起作用，并且它们可以作为增殖的标记物。
The cell cycle is a highly regulated and evolutionary conserved process that results in the duplication of cell content and the equal distribution of the duplicated chromosomes into a pair of daughter cells. Histones are fundamental structural components of chromatin in eukaryotic cells, and their post-translational modifications (PTMs) benchmark DNA readout and chromosome condensation. Aberrant regulation of cell cycle associated with dysregulation of histone PTMs is the cause of critical diseases such as cancer. Monitoring changes of histone PTMs could pave the way to understanding the molecular mechanisms associated with epigenetic regulation of cell proliferation. Previously, our lab established a novel middle-down workflow using porous graphitic carbon (PGC) as a stationary phase to analyze histone PTMs which utilizes the same reversed phase chromatography for gradient separation as canonical proteomics coupled with on-line MS. Here, we applied this novel workflow for high-throughput analysis of histone modifications of H3.1 and H3.2 during cell cycle. Collectively, we identified 1133 uniquely modified canonical histone H3 N-terminal tails. Consistent with previous findings, histone H3 phosphorylation increased significantly during M phase. Histone H3 variant-specific and cell cycle-depend expressions of PTMs were observed, underlining the need to not combine H3.1 and H3.2 together as H3. We confirmed previously known H3 PTM crosstalk (e.g. K9me-S10ph) and revealed new information in this area as well. These findings imply that the combinatorial PTMs play a role in cell cycle control and they may serve as markers for proliferation.
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影响因子：
14.8
作者：
Garcia, Benjamin A.;Mollah, Sahana;Hunt, Donald F.
通讯作者：
Hunt, Donald F.
DOI：
10.1038/nrg3673
发表时间：
2014-04
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.4
作者：
Jiang T;Hoover ME;Holt MV;Freitas MA;Marshall AG;Young NL
通讯作者：
Young NL
DOI：
10.1073/pnas.0600803103
发表时间：
2006-04-25
影响因子：
11.1
作者：
Hake, SB;Allis, CD
通讯作者：
Allis, CD
影响因子：
4.8
作者：
Duan, Qing;Chen, Haobin;Dai, Wei
通讯作者：
Dai, Wei