CENP-A K124 Ubiquitylation Is Required for CENP-A Deposition at the Centromere

Niikura, Yohei; Kitagawa, Risa; Ogi, Hiroo; Abdulle, Rashid; Pagala, Vishwajeeth; Kitagawa, Katsumi

doi:10.1016/j.devcel.2015.01.024

Cited by 95 publications

(141 citation statements)

References 65 publications

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“…After acceptance of this work for publication, it has come to the attention of the authors the recent work by Niikura et al (2015), who report that CRL4 in complex with COPS8/CSN8 is also required for CENP-A centromeric localization.…”

Section: Note Added In Proofmentioning

confidence: 99%

CRL4RBBP7 is required for efficient CENP-A deposition at centromeres

Mouysset¹,

Gilberto²,

Meier³

et al. 2015

Journal of Cell Science

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The mitotic spindle drives chromosome movement during mitosis and attaches to chromosomes at dedicated genomic loci named centromeres. Centromeres are epigenetically specified by their histone composition, namely the presence of the histone H3 variant CENP-A, which is regulated during the cell cycle by its dynamic expression and localization. Here, we combined biochemical methods and quantitative imaging approaches to investigate a new function of CUL4-RING E3 ubiquitin ligases (CRL4) in regulating CENP-A dynamics. We found that the core components CUL4 and DDB1 are required for centromeric loading of CENP-A, but do not influence CENP-A maintenance or pre-nucleosomal CENP-A levels. Interestingly, we identified RBBP7 as a substrate-specific CRL4 adaptor required for this process, in addition to its role in binding and stabilizing soluble CENP-A. Our data thus suggest that the CRL4 complex containing RBBP7 (CRL4 RBBP7 ) might regulate mitosis by promoting ubiquitin-dependent loading of newly synthesized CENP-A during the G1 phase of the cell cycle.

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Section: Note Added In Proofmentioning

confidence: 99%

CRL4RBBP7 is required for efficient CENP-A deposition at centromeres

Mouysset¹,

Gilberto²,

Meier³

et al. 2015

Journal of Cell Science

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“…In contrast, monoubiquitination is a stable protein modification. So far, H3 ubiquitination has only been reported for centromeric H3 variants in yeast and mammals (Hewawasam et al, 2010;Niikura et al, 2015). Monoubiquitination of H2A and H2B and their role in activating gene expression and PRC2 silencing, respectively, are well established (Weake and Workman, 2008).…”

Section: Discussionmentioning

confidence: 99%

A JUMONJI Protein with E3 Ligase and Histone H3 Binding Activities Affects Transposon Silencing in Arabidopsis

et al. 2016

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Transposable elements (TEs) make up a large proportion of eukaryotic genomes. As their mobilization creates genetic variation that threatens genome integrity, TEs are epigenetically silenced through several pathways, and this may spread to neighboring sequences. JUMONJI (JMJ) proteins can function as antisilencing factors and prevent silencing of genes next to TEs. Whether TE silencing is counterbalanced by the activity of antisilencing factors is still unclear. Here, we characterize JMJ24 as a regulator of TE silencing. We show that loss of JMJ24 results in increased silencing of the DNA transposon AtMu1c, while overexpression of JMJ24 reduces silencing. JMJ24 has a JumonjiC (JmjC) domain and two RING domains. JMJ24 autoubiquitinates in vitro, demonstrating E3 ligase activity of the RING domain(s). JMJ24-JmjC binds the N-terminal tail of histone H3, and full-length JMJ24 binds histone H3 in vivo. JMJ24 activity is anticorrelated with histone H3 Lys 9 dimethylation (H3K9me2) levels at AtMu1c. Double mutant analyses with epigenetic silencing mutants suggest that JMJ24 antagonizes histone H3K9me2 and requires H3K9 methyltransferases for its activity on AtMu1c. Genome-wide transcriptome analysis indicates that JMJ24 affects silencing at additional TEs. Our results suggest that the JmjC domain of JMJ24 has lost demethylase activity but has been retained as a binding domain for histone H3. This is in line with phylogenetic analyses indicating that JMJ24 (with the mutated JmjC domain) is widely conserved in angiosperms. Taken together, this study assigns a role in TE silencing to a conserved JmjC-domain protein with E3 ligase activity, but no demethylase activity.

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“…While the CENP-A CATD is sufficient to bind HJURP and directs CENP-A deposition to centromeres, the posttranslational modifications of two evolutionarily conserved residues, Ser-68 and Lys-124, that lie outside the CATD, have been demonstrated to affect CENP-A localization at the centromeres, although the functional aspects of these modifications remain a point of dispute and are discussed below (Hu et al 2011; Niikura et al 2015; Wang et al 2017; Yu et al 2015). More recently, another modification, Ser-18 phosphorylation that also exists outside CATD has been shown to negatively regulate CENP-A deposition (Takada et al 2017).…”

Section: Cenp-a Posttranslational Modifications and Deposition At Cenmentioning

confidence: 99%

“…3) (Niikura et al 2015). The SGT1-HSP90 complex facilitates the recognition of CENP-A by COPS8 and Lys-124 undergoes ubiquitylation by the CUL4A-RBX1-COPS8 complex (Niikura et al 2016; Niikura et al 2015; Niikura et al 2017b) (Fig. 3).…”

Section: Cenp-a Posttranslational Modifications and Deposition At Cenmentioning

confidence: 99%

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Posttranslational modifications of CENP-A: marks of distinction

Srivastava

Foltz

2018

Chromosoma

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Centromeres are specialized chromosome domain that serve as the site for kinetochore assembly and microtubule attachment during cell division, to ensure proper segregation of chromosomes. In higher eukaryotes, the identity of active centromeres is marked by the presence of CENP-A (centromeric protein-A), a histone H3 variant. CENP-A forms a centromere-specific nucleosome that acts as a foundation for centromere assembly and function. The posttranslational modification (PTM) of histone proteins is a major mechanism regulating the function of chromatin. While a few CENP-A site-specific modifications are shared with histone H3, the majority are specific to CENP-A-containing nucleosomes, indicating that modification of these residues contribute to centromere-specific function. CENP-A undergoes posttranslational modifications including phosphorylation, acetylation, methylation, and ubiquitylation. Work from many laboratories have uncovered the importance of these CENP-A modifications in its deposition at centromeres, protein stability, and recruitment of the CCAN (constitutive centromere-associated network). Here, we discuss the PTMs of CENP-A and their biological relevance.

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CENP-A K124 Ubiquitylation Is Required for CENP-A Deposition at the Centromere

Cited by 95 publications

References 65 publications

CRL4RBBP7 is required for efficient CENP-A deposition at centromeres

CRL4RBBP7 is required for efficient CENP-A deposition at centromeres

A JUMONJI Protein with E3 Ligase and Histone H3 Binding Activities Affects Transposon Silencing in Arabidopsis

Posttranslational modifications of CENP-A: marks of distinction

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