專題：Science系列
2010年4月2日，北京生命科學研究所(NIBS)朱冰實驗室在science雜誌發表文章，報導了DNA複製過程中核小體裝配的方式。
真核生物DNA與包括組蛋白在內的多種蛋白質組裝成為染色質，染色質的結構給基因功能提供了遺傳信息之外的另一層次的調控方式。核小體是染色質的基礎結構單元，它由DNA與組蛋白八聚體包裝而成，其中H3-H4構成組蛋白核心四聚體。組蛋白H3-H4攜帶的一系列穩定修飾被認為可在有絲分裂細胞周期中得到繼承，起到表觀遺傳信息的作用，但是這些修飾的繼承方式尚有待研究。想要發掘組蛋白修飾的繼承機理，就必須首先澄清DNA複製過程中核小體結構的分配模式。
NIBS朱冰實驗室與蛋白質中心合作，利用基於穩定同位素標記的定量質譜技術對DNA複製之後「新」、「舊」組蛋白的分配進行研究。作者以可誘導表達融合FLAG標籤的組蛋白H3.1和H3.3的哺乳動物細胞系作為模式體系開展實驗。在本項工作中，作者們發現H3.1-H4組成的核心四聚體在DNA複製過程中保持完整。此結果暗示，新的組蛋白H3.1-H4可能以相鄰核小體的已有修飾為模板，重新建立其修飾模式。作者們還首次發現由組蛋白變體H3.3組成的H3-H4四聚體會發生相當量的「新」、「舊」重組。這種重組的生物學意義值得進一步探究。
NIBS博士生徐墨與技術員龍承祖為本文的共同第一作者，其他作者還有研究生陳秀珍和黃暢。朱冰博士和陳涉博士為文章的共同通訊作者。此項研究由科技部863計劃和北京市科委資助，在北京生命科學研究所完成。
論文「Partition of histone H3/H4 tetramers during DNA replication dependent chromatin assembly」引起關注，science配發了Geneviève Almouzni博士題名為「Mixing or not mixing」的文章,對此項工作進行了評論與展望。評論指出「儘管早期研究認為，組蛋白H2A-H2B可以在核小體之間交換而H3-H4四聚體保持穩定，但是近年關於新合成的H3-H4以二聚體形式與histone chaperone組裝的發現重新激起了爭論」，作者們的研究工作「確鑿了關於舊的組蛋白H3-H4四聚體保持穩定的早期研究」，同時還發現「組蛋白變體H3.3與H4形成的四聚體在細胞周期中可以發生分裂」。該評論認為「下一步的挑戰在於，探究這些核小體重組模式是如何與組蛋白修飾的繼承方式相關聯的」以及「細胞是如何做出重組與否的選擇，而這種選擇是否在細胞生命和個體發育過程中被調控」。(生物谷Bioon.com)
Human Mutation：線粒體DNA複製研究新發現
Nature：DNA複製雙鏈同時完成機制
PNAS：單分子分析揭示DNA複製
生物谷推薦原文出處：
Science 2 April 2010 DOI: 10.1126/science.1178994
Partitioning of Histone H3-H4 Tetramers During DNA Replication–Dependent Chromatin Assembly
Mo Xu,1,2,* Chengzu Long,2,* Xiuzhen Chen,3,2 Chang Huang,4,2 She Chen,2, Bing Zhu2,
Semiconservative DNA replication ensures the faithful duplication of genetic information during cell divisions. However, how epigenetic information carried by histone modifications propagates through mitotic divisions remains elusive. To address this question, the DNA replication–dependent nucleosome partition pattern must be clarified. Here, we report significant amounts of H3.3-H4 tetramers split in vivo, whereas most H3.1-H4 tetramers remained intact. Inhibiting DNA replication–dependent deposition greatly reduced the level of splitting events, which suggests that (i) the replication-independent H3.3 deposition pathway proceeds largely by cooperatively incorporating two new H3.3-H4 dimers and (ii) the majority of splitting events occurred during replication-dependent deposition. Our results support the idea that "silent" histone modifications within large heterochromatic regions are maintained by copying modifications from neighboring preexisting histones without the need for H3-H4 splitting events.
1 Graduate Program, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, People’s Republic of China.
2 National Institute of Biological Sciences, 7 Science Park Road, Zhong Guan Cun Life Science Park, Beijing 102206, People’s Republic of China.
3 Life Science College, Beijing Normal University, Beijing 100875, People’s Republic of China.
4 Department of Biochemistry, College of Biological Sciences, China Agricultural University, Beijing 100094, People’s Republic of China.
Dominique Ray-Gallet and Geneviève Almouzni 評論摘要：
Mixing or Not Mixing
Beyond DNA information, the organization of the proteins and DNA that constitute chromatin represents a means to regulate genome function (1). The inheritance and maintenance of the DNA sequence has been explained by a semiconservative mechanism of replication in which a complementary new strand of DNA is synthesized along each parental strand, resulting in an inherited double-stranded molecule that contains old and new DNA. But how is the inheritance of epigenetic traits—modifications of chromatin proteins (histones) and DNA that do not alter the sequence—affected by dynamic changes in chromatin organization during eukaryotic cell division? On page 94 of this issue, Xu et al. (2) explore how parental (old) and newly synthesized histones associate after replication.