Nakatani Y, Tagami H, Shestakova E
Dana-Farber Cancer Institute and Harvard Medical School, MA, Boston 02115, USA.
Ernst Schering Res Found Workshop. 2006(57):89-96. doi: 10.1007/3-540-37633-x_5.
Although most somatic cells have identical genetic information, gene expression profiles are quite distinct in each cell type. The gene expression profiles are considered to be determined mainly by chromatin-encoded epigenetic information that includes histone modifications, histone variants, and factors such as HP1 and polycomb group proteins that organize higher-ordered chromatin structures. To gain insights into how such epigenetic information on chromatin is inherited on daughter DNA strands after DNA replication, we have purified the preassembled form of histone H3 by immunoaffinity purification. The histone H3 complex contains the two histone H3-H4 chaperones CAF1 and ASF1. Surprisingly, the H3 complex also contains a pair of H3-H4 dimers. This observation is striking because histones H3-H4 are known to exist as tetramers in solution. Since histones H3-H4 in the predeposition complex exist as a dimer, this raises the possibility that the H3-H4 dimer in the complex pairs with a parental H3-H4 dimer, assembling the de novo-synthesized and parental H3-H4 dimers in the same nucleosome. Based on these results, we propose a semi-conservative model of nucleosome duplication, which allows for segregation of parental H3-H4 dimers with encoded epigenetic information evenly to daughter DNA strands.
尽管大多数体细胞具有相同的遗传信息，但基因表达谱在每种细胞类型中却截然不同。基因表达谱被认为主要由染色质编码的表观遗传信息决定，这些信息包括组蛋白修饰、组蛋白变体以及诸如HP1和多梳蛋白家族等组织高阶染色质结构的因子。为了深入了解DNA复制后染色质上的这种表观遗传信息如何在子代DNA链上遗传，我们通过免疫亲和纯化法纯化了预组装形式的组蛋白H3。组蛋白H3复合物包含两个组蛋白H3-H4伴侣蛋白CAF1和ASF1。令人惊讶的是，H3复合物还包含一对H3-H4二聚体。这一观察结果令人瞩目，因为已知组蛋白H3-H4在溶液中以四聚体形式存在。由于预沉积复合物中的组蛋白H3-H4以二聚体形式存在，这就增加了复合物中的H3-H4二聚体与亲本H3-H4二聚体配对的可能性，从而在同一个核小体中组装新生合成的和亲本的H3-H4二聚体。基于这些结果，我们提出了一种核小体复制的半保留模型，该模型允许带有编码表观遗传信息的亲本H3-H4二聚体均匀地分离到子代DNA链上。
