Two distinct modes for propagation of histone PTMs across the cell cycle.
Two distinct modes for propagation of histone PTMs across the cell cycle.
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DOI：
10.1101/gad.256354.114
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发表时间：
2015-03-15
影响因子：
10.5
通讯作者：
Groth A
中科院分区：
文献类型：
--
作者：
Alabert C;Barth TK;Reverón-Gómez N;Sidoli S;Schmidt A;Jensen ON;Imhof A;Groth A
由染色质定义的表观遗传状态可以通过有丝分裂细胞分裂来维持。Albertert等人追踪了DNA复制过程中和整个细胞周期中的组蛋白修饰和组蛋白变体，发现翻译后修饰（PTM）与亲本组蛋白一起传递到新复制的DNA。二甲基化和三甲基化标记在DNA复制时被稀释两倍，但在一个细胞周期内，所有PTM都被恢复。H3K9me3和H3K27me3通过亲本和新组蛋白的连续修饰而繁殖，因为这些标记的建立持续了几代细胞。由染色质定义的表观遗传状态可以通过有丝分裂细胞分裂来维持。然而，仍然不知道基于组蛋白的信息是如何传递的。在这里，我们结合联合收割机新生染色质捕获（NCC）和三重SILAC（稳定同位素标记与氨基酸在细胞培养）标记跟踪组蛋白修饰和组蛋白变体在DNA复制和整个细胞周期。我们发现，翻译后修饰（PTM）与亲本组蛋白传递到新复制的DNA。由于新的组蛋白沉积，二甲基化和三甲基化标记在DNA复制时被稀释两倍。重要的是，在一个细胞周期内，所有的PTM都被恢复。通常，新的组蛋白被修饰以反映亲本组蛋白。然而，H3K9三甲基化（H3K9me3）和H3K27me3通过亲本和新组蛋白的连续修饰而繁殖，因为这些标记的建立跨越几代细胞。总之，我们的研究结果揭示了组蛋白标记如何传播，并表明染色质状态在细胞周期内振荡。
Epigenetic states defined by chromatin can be maintained through mitotic cell division. Alabert et al. tracked histone modifications and histone variants during DNA replication and across the cell cycle and found that post-translational modifications (PTMs) are transmitted with parental histones to newly replicated DNA. Di- and tri-methylation marks are diluted two-fold upon DNA replication, but within one cell cycle all PTMs are restored. H3K9me3 and H3K27me3 are propagated by continuous modification of parental and new histones, because the establishment of these marks extends over several cell generations. Epigenetic states defined by chromatin can be maintained through mitotic cell division. However, it remains unknown how histone-based information is transmitted. Here we combine nascent chromatin capture (NCC) and triple-SILAC (stable isotope labeling with amino acids in cell culture) labeling to track histone modifications and histone variants during DNA replication and across the cell cycle. We show that post-translational modifications (PTMs) are transmitted with parental histones to newly replicated DNA. Di- and trimethylation marks are diluted twofold upon DNA replication, as a consequence of new histone deposition. Importantly, within one cell cycle, all PTMs are restored. In general, new histones are modified to mirror the parental histones. However, H3K9 trimethylation (H3K9me3) and H3K27me3 are propagated by continuous modification of parental and new histones because the establishment of these marks extends over several cell generations. Together, our results reveal how histone marks propagate and demonstrate that chromatin states oscillate within the cell cycle.
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