Structural transitions of centromeric chromatin regulate the cell cycle-dependent recruitment of CENP-N

Fang, Junshun; 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

doi:10.1101/gad.259432.115

Cited by 66 publications

(85 citation statements)

References 61 publications

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“…The CENP-N N-terminal region (residues 1 to 286 in humans) is responsible for recognition of the CENP-A nucleosome (7, 8), whereas its C-terminal region (residues 287 to 339) interacts with the CCAN through CENP-L (9, 10). The recruitment of CENP-N to the centromere requires recognition of the L1 loop of CENP-A (11). …”

mentioning

confidence: 99%

Structural mechanisms of centromeric nucleosome recognition by the kinetochore protein CENP-N

Chittori

Hong²,

Saunders³

et al. 2018

Science

107

146

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Accurate chromosome segregation requires the proper assembly of kinetochore proteins. A key step in this process is the recognition of the histone H3 variant CENP-A in the centromeric nucleosome by the kinetochore protein CENP-N. We report cryo–electron microscopy (cryo-EM), biophysical, biochemical, and cell biological studies of the interaction between the CENP-A nucleosome and CENP-N. We show that human CENP-N confers binding specificity through interactions with the L1 loop of CENP-A, stabilized by electrostatic interactions with the nucleosomal DNA. Mutational analyses demonstrate analogous interactions in Xenopus, which are further supported by residue-swapping experiments involving the L1 loop of CENP-A. Our results are consistent with the coevolution of CENP-N and CENP-A and establish the structural basis for recognition of the CENP-A nucleosome to enable kinetochore assembly and centromeric chromatin organization.

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mentioning

confidence: 99%

Structural mechanisms of centromeric nucleosome recognition by the kinetochore protein CENP-N

Chittori

Hong²,

Saunders³

et al. 2018

Science

107

146

View full text Add to dashboard Cite

show abstract

“…This situation creates separate hierarchies during de novo CCAN recruitment and for maintenance of CCAN components at various cell cycle stages. CENP-C and CENP-N bind directly to CENP-A nucleosomes in vitro (Carroll et al 2009(Carroll et al , 2010Kato et al 2013;Falk et al 2015Falk et al , 2016Fang et al 2015) and localize near the CENP-A chromatin in vivo (Fig. 3a) (Wan et al 2009).…”

Section: Cenp-c Functions Upstream Of Other Ccan Components During Dementioning

confidence: 93%

“…Recent studies suggest that there is no clear hierarchy for CCAN recruitment and maintenance (Hori et al 2008a;Fang et al 2015;McKinley et al 2015;Nagpal et al 2015), although there are active debates about this issue (Carroll et al 2010;Basilico et al 2014;Klare et al 2015). Various dynamic interactions between the different CCAN sub-complexes result in an extensive meshwork of interactions ( Fig.…”

Section: Cenp-c Functions Upstream Of Other Ccan Components During Dementioning

confidence: 97%

Kinetochore assembly and function through the cell cycle

Nagpal

Fukagawa

2016

Chromosoma

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The kinetochore is an essential structure for the chromosome segregation machinery in eukaryotes; it serves as a bridge between the spindle microtubules and chromosomes. The kinetochore consists of multiple interconnecting components on the centromere; therefore, understanding its formation, molecular function, and regulation has remained an ongoing challenge. Recent studies have provided new insights into centromere identity, kinetochore assembly, and function. In this review, we discuss recent advances in our understanding of the function and regulation of key kinetochore components. We highlight the reciprocal localization dependencies of the different sub-complexes of the kinetochore and describe their regulation during the cell cycle.

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“…By using biochemical, biophysical, and cell-based assays, we showed that the RG loop, the two CENP-A-specific residues Arg80 and Gly81 in loop1 located at the lateral surface of CENP-A nucleosome (Tachiwana et al 2011), not only provides the recognition site for the binding of CENP-N to the CENP-A nucleosome, but also facilitates the folding of CENP-A arrays into a compact "ladder-like" chromatin structure in the presence of MgCl 2 , as revealed by AUC and EM analyses ( Fig. 5A-C ;Fang et al 2015). Interestingly, we found that the formation of a compact "ladder-like" structure of CENP-A chromatin inhibits the binding and recruitment of CENP-N through concealing/hiding the RG loop within chromatin fiber.…”

Section: Epigenetic Regulation Of Chromatin Fibers By Chromatin Factorsmentioning

confidence: 97%

Structure and Epigenetic Regulation of Chromatin Fibers

Chen

2017

Cold Spring Harb Symp Quant Biol

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In eukaryotes, genomic DNA is hierarchically packaged by histones into chromatin on several levels to fit inside the nucleus. As a central-level structure between nucleosomal arrays and higher-order chromatin organizations, the 30-nm chromatin fiber and its dynamics play a crucial role in gene regulation. However, despite considerable efforts over the past three decades, the fundamental structure and its dynamic regulation of chromatin fibers still remain as a big challenge in molecular biology. Here, we mainly summarize the most recent progress in elucidating the structure of the 30-nm chromatin fiber in vitro and epigenetic regulation of chromatin fibers by chromatin factors, particularly histone variants. In addition, we also discuss recent studies in unraveling the three-dimensional organization of chromatin fibers in situ by genomic approaches and electron microscopy.In eukaryotic cells, the accessibility of DNA is dependent on the packing density of chromatin fibers. Genomic DNA firstly wraps around a histone octamer to form a nucleosome, which is connected by linker DNA to form the primary chromatin structure, the "beads-on-a-string" nucleosomal array. Nucleosomes in the array are further compacted by linker histone H1 to form a 30-nm chromatin fiber-typically regarded as the secondary structure of chromatin. Chromatin fibers are further organized into other higher-levels of chromatin structures, but so far details of these structural levels still remain obscure. The three-dimensional (3D) organization of genomic DNA plays a critical role in regulating DNA-related biological processes, such as gene transcription and DNA replication, repair, and recombination. Elucidating the structure and dynamics of chromatin fibers in molecular details is the key to understanding the epigenetic regulation of gene expression by different chromatin factors. HIGH-RESOLUTION STRUCTURE OF 30-NM CHROMATIN FIBERSIt is still a puzzle how genomic DNA is hierarchically organized in eukaryotic cells. From a structural point of view, the DNA double-helix structure discovered by Watson and Crick is surely the most important milestone in molecular biology (Watson and Crick 1953). After more than 40 years, the high-resolution structure of the nucleosome core particle (NCP) has been defined by crystal Xray studies (Luger et al. 1997), which undoubtedly reveals the structural details of histone-histone and histone-DNA interactions within nucleosomes (Fig. 1). Other high-resolution structures of NCPs containing core histones from different species or with a different DNA sequence, different histone variants, or different nucleosome-binding proteins/peptides have been resolved subsequently to investigate the regulation of nucleosome structure as reviewed previously (Cutter and Hayes 2015;McGinty and Tan 2015;Zhu and Li 2016).Afterward, the manner of how a "beads-on-a-string" nucleosomal array folds into a condensed 30-nm chromatin fiber remains to be determined. Two basic classes of structural models had been proposed previously based on ...

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Structural transitions of centromeric chromatin regulate the cell cycle-dependent recruitment of CENP-N

Cited by 66 publications

References 61 publications

Structural mechanisms of centromeric nucleosome recognition by the kinetochore protein CENP-N

Structural mechanisms of centromeric nucleosome recognition by the kinetochore protein CENP-N

Kinetochore assembly and function through the cell cycle

Structure and Epigenetic Regulation of Chromatin Fibers

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