Subjects: Biology >> Biophysics >> Cell Biology submitted time 2016-05-12
Yu, Zhouliang
Zhou, Xiang
Wang, Wenjing
Deng, Wenqiang
Fang, Junnan
Hu, Hao
Wang, Zichen
Cui, Lei
Shen, Jing
Ou, Guangshuo
Yang, Na
Chen, Ping
Xu, Rui-Ming
Li, Guohong
Yu, Zhouliang
Deng, Wenqiang
Fang, Junnan
Hu, Hao
Peng, Shengyi
Li, Shangze
Abstract： The H3 histone variant CENP-A is an epigenetic marker critical for the centromere identity and function. However, the precise regulation of the spatiotemporal deposition and propagation of CENP-A at centromeres during the cell cycle is still poorly understood. Here, we show that CENP-A is phosphorylated at Ser68 during early mitosis by Cdk1. Our results demonstrate that phosphorylation of Ser68 eliminates the binding of CENP-A to the assembly factor HJURP, thus preventing the premature loading of CENP-A to the centromere prior to mitotic exit. Because Cdk1 activity is at its minimum at the mitotic exit, the ratio of Cdk1/PP1 alpha activity changes in favor of Ser68 dephosphorylation, thus making CENP-A available for centromeric deposition by HJURP. Thus, we reveal that dynamic phosphorylation of CENP-A Ser68 orchestrates the spatiotemporal assembly of newly synthesized CENP-A at active centromeres during the cell cycle.
Peer Review Status:
Awaiting Review
Subjects: Biology >> Biophysics >> Cell Biology submitted time 2016-05-12
Fang, Junnan
Liu, Yuting
Wei, Yun
Deng, Wenqiang
Yu, Zhouliang
Huang, Li
Teng, Yan
Yao, Ting
You, Qinglong
Ruan, Haihe
Chen, Ping
Xu, Rui-Ming
Li, Guohong
Fang, Junnan
Liu, Yuting
Deng, Wenqiang
Yu, Zhouliang
You, Qinglong
Abstract： Specific recognition of centromere-specific histone variant CENP-A-containing chromatin by CENP-N is an essential process in the assembly of the kinetochore complex at centromeres prior to mammalian cell division. However, the mechanisms of CENP-N recruitment to centromeres/kinetochores remain unknown. Here, we show that a CENP-A-specific RG loop (Arg80/Gly81) plays an essential and dual regulatory role in this process. The RG loop assists the formation of a compact "ladder-like" structure of CENP-A chromatin, concealing the loop and thus impairing its role in recruiting CENP-N. Upon G1/S-phase transition, however, centromeric chromatin switches from the compact to an open state, enabling the now exposed RG loop to recruit CENP-N prior to cell division. Our results provide the first insights into the mechanisms by which the recruitment of CENP-N is regulated by the structural transitions between compaction and relaxation of centromeric chromatin during the cell cycle.
Peer Review Status:Awaiting Review
Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology submitted time 2016-05-11
Abstract： Eukaryotic genomes are organized hierarchically into chromatin structures by histones. Despite extensive research for over 30 years, not only the fundamental structure of the 30-nm chromatin fiber is being debated, but the actual existence of such fiber remains hotly contested. In this review, we focus on the most recent progress in elucidating the structure of the 30-nm fiber upon in vitro reconstitution, and its possible organization inside the nucleus. In addition, we discuss the roles of linker histone H1 as well as the importance of specific nucleosome-nucleosome interactions in the formation of the 30-nm fiber. Finally, we discuss the involvement of structural variations and epigenetic mechanisms available for the regulation of this chromatin form. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Peer Review Status:Awaiting Review
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