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DNA介导的酵母染色质组装因子1（CAF-1）的两个组蛋白结合复合物的缔合在DNA复制后驱动四体组装。

DNA-mediated association of two histone-bound complexes of yeast Chromatin Assembly Factor-1 (CAF-1) drives tetrasome assembly in the wake of DNA replication.

作者信息

Mattiroli Francesca, Gu Yajie, Yadav Tejas, Balsbaugh Jeremy L, Harris Michael R, Findlay Eileen S, Liu Yang, Radebaugh Catherine A, Stargell Laurie A, Ahn Natalie G, Whitehouse Iestyn, Luger Karolin

机构信息

Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, United States.

Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, United States.

出版信息

Elife. 2017 Mar 18;6:e22799. doi: 10.7554/eLife.22799.

DOI:10.7554/eLife.22799
PMID:28315523
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5404915/
Abstract

Nucleosome assembly in the wake of DNA replication is a key process that regulates cell identity and survival. Chromatin assembly factor 1 (CAF-1) is a H3-H4 histone chaperone that associates with the replisome and orchestrates chromatin assembly following DNA synthesis. Little is known about the mechanism and structure of this key complex. Here we investigate the CAF-1•H3-H4 binding mode and the mechanism of nucleosome assembly. We show that yeast CAF-1 binding to a H3-H4 dimer activates the Cac1 winged helix domain interaction with DNA. This drives the formation of a transient CAF-1•histone•DNA intermediate containing two CAF-1 complexes, each associated with one H3-H4 dimer. Here, the (H3-H4) tetramer is formed and deposited onto DNA. Our work elucidates the molecular mechanism for histone deposition by CAF-1, a reaction that has remained elusive for other histone chaperones, and it advances our understanding of how nucleosomes and their epigenetic information are maintained through DNA replication.

摘要

DNA复制之后的核小体组装是一个调控细胞特性与存活的关键过程。染色质组装因子1（CAF-1）是一种H3-H4组蛋白伴侣，它与复制体相关联，并在DNA合成后协调染色质组装。对于这个关键复合物的机制和结构知之甚少。在此，我们研究CAF-1与H3-H4的结合模式以及核小体组装的机制。我们发现酵母CAF-1与H3-H4二聚体的结合激活了Cac1翼状螺旋结构域与DNA的相互作用。这驱动形成了一个包含两个CAF-1复合物的瞬时CAF-1•组蛋白•DNA中间体，每个复合物与一个H3-H4二聚体相关联。在此，（H3-H4）四聚体形成并沉积到DNA上。我们的工作阐明了CAF-1进行组蛋白沉积的分子机制，这一反应对于其他组蛋白伴侣来说一直难以捉摸，并且增进了我们对核小体及其表观遗传信息如何通过DNA复制得以维持的理解。

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