Centromeric chromatin exhibits a histone modification pattern that is distinct from both euchromatin and heterochromatin

Sullivan, Beth A.; Karpen, Gary H.

doi:10.1038/nsmb845

Cited by 518 publications

(627 citation statements)

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“…Classically, centromeres were assumed to be composed of heterochromatin. However, the groundbreaking study of Sullivan and Karpen revealed that the kinetochorespecific histone CENP-A resides in a specialized chromatin environment, which has been termed 'centrochromatin' (Sullivan and Karpen, 2004). A more recent study has shown that centrochromatin has a histone modification pattern resembling that found in the downstream body of transcribed genes (Bergmann et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Besides CENP-A, active centromeres display a specific profile of post-translational modifications on their associated histone H3-containing nucleosomes (Bergmann et al, 2011;Lam et al, 2006;Ribeiro et al, 2010;Sullivan and Karpen, 2004). This special chromatin, which has been termedx 'centrochromatin' (Sullivan and Karpen, 2004), suggests a functional link between the local chromatin environment and kinetochore function.…”

Section: Introductionmentioning

confidence: 99%

“…This special chromatin, which has been termedx 'centrochromatin' (Sullivan and Karpen, 2004), suggests a functional link between the local chromatin environment and kinetochore function. Indeed, previous work from our laboratories indicates that the local chromatin state is crucial for the maintenance of a functional kinetochore structure (Bergmann et al, 2011;Cardinale et al, 2009;Nakano et al, 2008;Nakano et al, 2003;Nakashima et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…Importantly, although H3K4 methylation was considered a mark of euchromatin, it is present at heterochromatic centromeric DNA in fission yeast, Drosophila, and human cells (Sullivan and Karpen 2004;Cam et al 2005). Diminished levels of H3K4 methylation affects the recruitment and deposition of the histone CENPA at centromeres of human artificial chromosomes, providing direct evidence for the involvement of Set1-mediated methylation in kinetochore function (Bergmann et al 2011).…”

Section: Set1 Complex Function Is Required With Nima For Normal Transmentioning

confidence: 99%

“…In fact, the kinetochore protein Hec1 (A. nidulans Ndc80) is phosphorylated by the human NIMA-related kinase, Nek2, thereby contributing to proper chromosome segregation (Chen et al 2002;Wei et al 2011). In addition, it is possible that deficiencies in Set1-mediated modulation of Aurora target phosphorylation (Zhang et al 2005) also contributes to the genetic interactions with NIMA.Importantly, although H3K4 methylation was considered a mark of euchromatin, it is present at heterochromatic centromeric DNA in fission yeast, Drosophila, and human cells (Sullivan and Karpen 2004;Cam et al 2005). Diminished levels of H3K4 methylation affects the recruitment and deposition of the histone CENPA at centromeres of human artificial chromosomes, providing direct evidence for the involvement of Set1-mediated methylation in kinetochore function (Bergmann et al 2011).…”

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confidence: 99%

The Set1/COMPASS Histone H3 Methyltransferase Helps Regulate Mitosis With the CDK1 and NIMA Mitotic Kinases in Aspergillus nidulans

et al. 2014

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Mitosis is promoted and regulated by reversible protein phosphorylation catalyzed by the essential NIMA and CDK1 kinases in the model filamentous fungus Aspergillus nidulans. Protein methylation mediated by the Set1/COMPASS methyltransferase complex has also been shown to regulate mitosis in budding yeast with the Aurora mitotic kinase. We uncover a genetic interaction between An-swd1, which encodes a subunit of the Set1 protein methyltransferase complex, with NIMA as partial inactivation of nimA is poorly tolerated in the absence of swd1. This genetic interaction is additionally seen without the Set1 methyltransferase catalytic subunit. Importantly partial inactivation of NIMT, a mitotic activator of the CDK1 kinase, also causes lethality in the absence of Set1 function, revealing a functional relationship between the Set1 complex and two pivotal mitotic kinases. The main target for Set1-mediated methylation is histone H3K4. Mutational analysis of histone H3 revealed that modifying the H3K4 target residue of Set1 methyltransferase activity phenocopied the lethality seen when either NIMA or CDK1 are partially functional. We probed the mechanistic basis of these genetic interactions and find that the Set1 complex performs functions with CDK1 for initiating mitosis and with NIMA during progression through mitosis. The studies uncover a joint requirement for the Set1 methyltransferase complex with the CDK1 and NIMA kinases for successful mitosis. The findings extend the roles of the Set1 complex to include the initiation of mitosis with CDK1 and mitotic progression with NIMA in addition to its previously identified interactions with Aurora and type 1 phosphatase in budding yeast.D URING the transition from interphase into mitosis, chromatin undergoes dramatic global restructuring to go from a relaxed interphase configuration amenable to gene expression to a condensed form characteristic of mitotic chromosomes. Chromatin condensation not only marks mitosis but is also essential for the normal segregation of the duplicated sister chromatids into daughter nuclei. On the other hand, during mitotic exit, decondensation of chromatin needs to be triggered in a correct temporal manner to enable successful transition into interphase. In Aspergillus nidulans, a model filamentous fungus that enabled discovery of cell cycle-specific genes, mitotic initiation requires the function of the essential NIMA mitotic kinase (Oakley and Morris 1983;Osmani et al. 1987). Early evidence pointed to a role for NIMA in regulating chromatin compaction through the cell cycle since overexpression of NIMA was sufficient to induce chromatin condensation independent of cell cycle phase (Osmani et al. 1988;. Importantly, NIMA is required for, and can promote, the phosphorylation of histone H3 at serine 10 (De Souza et al. 2000), a universal marker of mitotic chromatin. In addition, NIMA has been shown to regulate the partial disassembly of nuclear pore complexes, allowing the access of mitotic regulators to the nucleus (Wu et al. 1998;De S...

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Epigenetics of Filamentous Fungi

Smith

Phatale

Bredeweg

et al. 2012

Encyclopedia of Molecular Cell Biology and Molecular Medicine

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Centromeric chromatin exhibits a histone modification pattern that is distinct from both euchromatin and heterochromatin

Cited by 518 publications

References 37 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 Set1/COMPASS Histone H3 Methyltransferase Helps Regulate Mitosis With the CDK1 and NIMA Mitotic Kinases in Aspergillus nidulans

Epigenetics of Filamentous Fungi

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