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通过 CENP-N 解码着丝粒核小体。

Decoding the centromeric nucleosome through CENP-N.

机构信息

Department of Mechanistic Cell Biology, Max-Planck Institute of Molecular Physiology, Dortmund, Germany.

Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, United States.

出版信息

Elife. 2017 Dec 27;6:e33442. doi: 10.7554/eLife.33442.

DOI:10.7554/eLife.33442
PMID:29280735
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5777823/
Abstract

Centromere protein (CENP) A, a histone H3 variant, is a key epigenetic determinant of chromosome domains known as centromeres. Centromeres nucleate kinetochores, multi-subunit complexes that capture spindle microtubules to promote chromosome segregation during mitosis. Two kinetochore proteins, CENP-C and CENP-N, recognize CENP-A in the context of a rare CENP-A nucleosome. Here, we reveal the structural basis for the exquisite selectivity of CENP-N for centromeres. CENP-N uses charge and space complementarity to decode the L1 loop that is unique to CENP-A. It also engages in extensive interactions with a 15-base pair segment of the distorted nucleosomal DNA double helix, in a position predicted to exclude chromatin remodelling enzymes. Besides CENP-A, stable centromere recruitment of CENP-N requires a coincident interaction with a newly identified binding motif on nucleosome-bound CENP-C. Collectively, our studies clarify how CENP-N and CENP-C decode and stabilize the non-canonical CENP-A nucleosome to enforce epigenetic centromere specification and kinetochore assembly.

摘要

着丝粒蛋白 (CENP) A 是一种组蛋白 H3 变体，是一种关键的表观遗传决定因素，可将染色体结构域定义为着丝粒。着丝粒可启动动粒，这是一种多亚基复合物，可捕获纺锤体微管，以促进有丝分裂过程中的染色体分离。两种动粒蛋白 CENP-C 和 CENP-N 在罕见的 CENP-A 核小体背景下识别 CENP-A。在这里，我们揭示了 CENP-N 对着丝粒具有极高选择性的结构基础。CENP-N 利用电荷和空间互补性来解码 CENP-A 特有的 L1 环。它还与扭曲核小体 DNA 双螺旋的 15 个碱基对片段广泛相互作用，该位置预计可排除染色质重塑酶。除了 CENP-A，CENP-N 的稳定着丝粒募集还需要与核小体结合的 CENP-C 上新鉴定的结合基序同时发生相互作用。总的来说，我们的研究阐明了 CENP-N 和 CENP-C 如何解码和稳定非典型的 CENP-A 核小体，以强制建立表观遗传的着丝粒特征和动粒组装。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6c7/5777823/36bea0a9270a/elife-33442-fig6.jpg
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3
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4
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