Priming of Centromere for CENP-A Recruitment by Human hMis18α, hMis18β, and M18BP1

Fujita, Yohta; Hayashi, Takeshi; Kiyomitsu, Tomomi; Toyoda, Yusuke; Kokubu, Aya; Obuse, Chikashi; Yanagida, Mitsuhiro

doi:10.1016/j.devcel.2006.11.002

Cited by 369 publications

(657 citation statements)

References 35 publications

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“…Given the historic assumptions about the links between centromeres and heterochromatin, it might seem surprising that kinetochore chromatin appears to be more tolerant of an 'open' state, defined by high levels of acetylation and partial decondensation, than a 'closed' and/or repressive state. However, it has been known for a number of years that the Mis18 complex, which is associated with CENP-A loading, is associated with acetyltransferase activity (Fujita et al, 2007). Furthermore, recent work from our laboratories has revealed that H3K9 appears to function as an acetyl/methyl switch, regulating CENP-A loading by HJURP (Ohzeki et al, unpublished).…”

Section: Discussionmentioning

confidence: 99%

Epigenetic engineering: histone H3K9 acetylation is compatible with kinetochore structure and function

Bergmann

Jakubsche

Martins

et al. 2012

Journal of Cell Science

103

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SummaryHuman kinetochores are transcriptionally active, producing very low levels of transcripts of the underlying alpha-satellite DNA. However, it is not known whether kinetochores can tolerate acetylated chromatin and the levels of transcription that are characteristic of housekeeping genes, or whether kinetochore-associated 'centrochromatin', despite being transcribed at a low level, is essentially a form of repressive chromatin. Here, we have engineered two types of acetylated chromatin within the centromere of a synthetic human artificial chromosome. Tethering a minimal NF-kB p65 activation domain within kinetochore-associated chromatin produced chromatin with high levels of histone H3 acetylated on lysine 9 (H3K9ac) and an ,10-fold elevation in transcript levels, but had no substantial effect on kinetochore assembly or function. By contrast, tethering the herpes virus VP16 activation domain produced similar modifications in the chromatin but resulted in an ,150-fold elevation in transcripts, approaching the level of transcription of an endogenous housekeeping gene. This rapidly inactivated kinetochores, causing a loss of assembled CENP-A and blocking further CENP-A assembly. Our data reveal that functional centromeres in vivo show a remarkable plasticity -kinetochores tolerate profound changes to their chromatin environment, but appear to be critically sensitive to the level of centromeric transcription.

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Section: Discussionmentioning

confidence: 99%

Epigenetic engineering: histone H3K9 acetylation is compatible with kinetochore structure and function

Bergmann

Jakubsche

Martins

et al. 2012

Journal of Cell Science

103

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“…Eic1 may be the S. pombe homolog of Mis18BP1. Depletion of any one Mis18 complex component (apart from Eic2/Mis20) prevents new CENP-A assembly (Fujita et al 2007;Maddox et al 2007;Hayashi et al 2014;Subramanian et al 2014). However, in contrast to HJURP, overall cellular CENP-A levels are not diminished after Mis18 depletion, suggesting that the soluble HJURP:CENP-A:H4 remains stable without Mis18 activity and the Mis18 complex functions at chromatin rather than on soluble CENP-A.…”

Section: The Mis18 Complexmentioning

confidence: 87%

“…All three proteins interact but it is not known whether Mis18a, Mis18b, and M18BP1 function in CENP-A assembly exclusively as a complex. A homologous M18BP1 protein, Kinetochore Null 2 (KNL2), was discovered in a screen for kinetochore defects in C. elegans and M18BP1 has been identified in humans, Xenopus, and Arabidopsis (Fujita et al 2007;Maddox et al 2007;Moree et al 2011;Lermontova et al 2013). The function of the Mis18 complex remains unclear, and more proteins are likely to be involved.…”

Section: The Mis18 Complexmentioning

confidence: 99%

“…Mis18a, Mis18b, and M18BP1 are recruited to centromeres at an early stage in CENP-A assembly, during anaphase/telophase of mitosis and in early G 1 (Fujita et al 2007;Maddox et al 2007;Dambacher et al 2012). The Mis18 complex is required for the recruitment of HJURP to centromeres in a number of model organisms Williams et al 2009;Barnhart et al 2011;Moree et al 2011), and in human cells, depletion of HJURP has no effect on Mis18a.…”

Section: The Mis18 Complexmentioning

confidence: 99%

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The Centromere: Epigenetic Control of Chromosome Segregation during Mitosis

Westhorpe

Straight

2014

Cold Spring Harb Perspect Biol

149

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A fundamental challenge for the survival of all organisms is maintaining the integrity of the genome in all cells. Cells must therefore segregate their replicated genome equally during each cell division. Eukaryotic organisms package their genome into a number of physically distinct chromosomes, which replicate during S phase and condense during prophase of mitosis to form paired sister chromatids. During mitosis, cells form a physical connection between each sister chromatid and microtubules of the mitotic spindle, which segregate one copy of each chromatid to each new daughter cell. The centromere is the DNA locus on each chromosome that creates the site of this connection. In this review, we present a brief history of centromere research and discuss our current knowledge of centromere establishment, maintenance, composition, structure, and function in mitosis.

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“…We now know that mammalian cells address this issue by replenishing the CENP-A level per centromere in early G1 phase of the cell cycle, right after the previous round of genome division and before the next round of DNA replication. 2 Although several important stages and molecular players have been identified to license, load and stabilize newly synthesized CENP-A proteins at centromeres labeled with preexisted and diluted CENP-A, [3][4][5][6][7] a complete understanding is missing regarding how new CENP-A proteins become stably incorporated into centromeric nucleosomes during early G1.…”

mentioning

confidence: 99%

Formin-mediated epigenetic maintenance of centromere identity

Liu

Mao

2016

Small GTPases

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Accurate chromosome segregation in mammalian cells is guided by the centromere, a specialized chromosome region defined by the histone H3 variant centromere protein A (CENP-A). It is not well understood how cells maintain CENP-A levels at centromeres while continuously going through genome replications and cell divisions. A MgcRacGAP-dependent small GTPase molecular switch has been shown as essential for centromeric CENP-A maintenance. By using quantitative imaging, pulse-chase and live cell analysis, a recent work has suggested that the diaphanous formin mDia2, a well-established small GTPase effector, functions downstream of this small GTPase pathway to maintain CENP-A levels at centromeres. A constitutively active mDia2 construct is able to rescue the CENP-A loading defect caused by MgcRacGAP depletion. This study has uncovered an unsuspected role of the cytoskeleton protein mDia2 as an effector of the MgcRacGAP-dependent small GTPase signaling inside the nucleus to participate in the epigenetic regulation of centromere maintenance during cell cycle.

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Priming of Centromere for CENP-A Recruitment by Human hMis18α, hMis18β, and M18BP1

Cited by 369 publications

References 35 publications

Epigenetic engineering: histone H3K9 acetylation is compatible with kinetochore structure and function

Epigenetic engineering: histone H3K9 acetylation is compatible with kinetochore structure and function

The Centromere: Epigenetic Control of Chromosome Segregation during Mitosis

Formin-mediated epigenetic maintenance of centromere identity

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