Epigenetic engineering shows H3K4me2 is required for HJURP targeting and CENP-A assembly on a synthetic human kinetochore

Bergmann, Jan H.; Rodríguez, Mariluz Gómez; Martins, Nuno M. C.; Kimurâ, Hiroshi; Kelly, David A.; Masumoto, Hiroshi; Larionov, Vladimir; Jansen, Lars; Earnshaw, William C.

doi:10.1038/emboj.2010.329

Cited by 273 publications

(383 citation statements)

References 62 publications

Supporting

Mentioning

361

Contrasting

Unclassified

Order By: Relevance

“…While we are gaining a better understanding of the pathway that results in the assembly of CENP-A nucleosomes at centromeres, the precise mechanism for determining the genomic location of CENP-A deposition is unknown. Recent work implicates centromeric transcripts as active participants in CENP-A deposition and centromere function, adding complexity to a pathway previously thought to be restricted to a large protein network (Topp et al 2004;Chueh et al 2009;Ferri et al 2009;Bergmann et al 2011Bergmann et al , 2012. Historically, centromeres were considered simply heterochromatin-rich and thus transcriptionally silent.…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, transcripts emanating from both the pericentromere and centromere core have been identified in a multitude of organisms (Eymery et al 2009a;Stimpson and Sullivan 2010). Moreover, recent studies have identified proteins that interact with these transcripts (Topp et al 2004;Wong et al 2007;Chueh et al 2009;Ferri et al 2009;Du et al 2010;Hsieh et al 2011), analyzed the effects of increased and decreased transcription on genome stability (Bergmann et al 2011;Ohkuni and Kitagawa 2011;Bergmann et al 2012), or identified changes in transcription in stressed or diseased cells (Eymery et al 2009b;Gopalakrishnan et al 2009;Ting et al 2011;Zhu et al 2011). In this review, we will present pericentric and centromeric noncoding RNA transcription and discuss its diverse roles in modified histone recruitment, centromere function and stability, and insulator activity as well as newly discovered correlations between centromere and pericentromere transcription and human disease.…”

Section: Introductionmentioning

confidence: 99%

“…Densely packed heterochromatin is found in most eukaryotic pericentromeres, most commonly marked by di-and trimethylation of lysine residues 9 and 27 of histone H3 (H3K9me2, H3K9me3, H3K27me2, and H3K27me3), histone modifications typically associated with transcriptional silencing (Gopalakrishnan et al 2009). The chromatin encompassing the centromere core, also referred to as "centrochromatin," is distinct from that of pericentromeres and contains the histone H3 variant CENP-A interspersed with histone H3 methylation and dimethylation of lysine 4 and di-and trimethylation of lysine 36 of histone H3 (H3K4me1, H3K4me2, H3K36me2, and H3K36me3), histone modifications associated with transcriptionally active chromatin (Sullivan and Karpen 2004;Gopalakrishnan et al 2009;Bergmann et al 2011Bergmann et al , 2012. Interestingly, transcripts emanating from both the pericentromere and centromere core have been identified in a multitude of organisms (Eymery et al 2009a;Stimpson and Sullivan 2010).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pericentric and centromeric transcription: a perfect balance required

2012

View full text Add to dashboard Cite

The pericentromere and centromere regions of the genome have previously been considered tightly compacted and transcriptionally inert. However, there is mounting evidence that these regions not only actively produce transcripts but that these pericentric and centromeric transcripts are also vital to maintaining genome stability and proper cell division. In this review, we define the pericentromere and centromere of eukaryotic chromosomes in terms of their histone modifications and their nascent transcripts. In addition, we present the currently known roles these transcripts play in heterochromatin formation, development, and differentiation, as well as their interaction with centromeric proteins, and ultimately centromere function. Recent work has added considerable complexity to the theoretical framework defining the innate requirement for pericentric and centromeric transcription. It is clear that maintaining a fine balance of transcriptional output is critical, as deviations from this balance result in centromere disfunction and genomic instability.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pericentric and centromeric transcription: a perfect balance required

2012

View full text Add to dashboard Cite

show abstract

“…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). Therefore misregulation of centromere-kinetochore functions could contribute to the synthetic lethality and SAC-monitored mitotic defects in cells lacking adequate NIMA and Set1 complex function.…”

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

confidence: 99%

“…In addition, H3K4 methylation is also involved in maintaining the repression of telomere proximal genes in S. cerevisiae and Schizosaccharomyces pombe and the suppression of secondary metabolite production in A. nidulans and A. fumigatus (Krogan et al 2002;Kanoh et al 2003;Bok et al 2009;Palmer et al 2013). Growing evidence indicates that the Set1 complex is involved in a gamut of additional cellular functions, many of which may be independent of its roles in gene expression, including kinetochore maintenance, DNA repair, and replication checkpoints (Faucher and Wellinger 2010;Bergmann et al 2011). Importantly the Set1 complex regulates mitosis in budding yeast with the Aurora mitotic kinase Ipl1 and the type1 phosphatase Glc7 (Zhang et al 2005;Latham et al 2011).…”

mentioning

confidence: 99%

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

et al. 2014

View full text Add to dashboard Cite

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...

show abstract

Centromeres

Gohard

Zhiteneva

Earnshaw

2014

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Cell division requires the faithful partitioning of the replicated genome into two daughter cells. Failure to achieve this can result in cell death or drive neoplastic transformation and, in meiosis, can lead to infertility and aneuploidy. Centromeres are sites at which eukaryotic chromosomes interact with the mitotic spindle and sister chromatids remain linked until properly aligned. Linkage to the spindle occurs via the kinetochore – a highly elaborate proteinaceous structure assembled on the surface of the centromere. Paradoxically given their essential functions, there is a surprising diversity in centromeric architecture, deoxyribonucleic acid (DNA) sequence and protein composition across eukaryotes. Centromere assembly and maintenance are epigenetically determined, and their key unifying feature is the presence of a centromere‐specific histone H3 variant: CENP‐A. In this article, the authors have focused on the specification, composition and function of the mammalian centromere in mitosis. Key Concepts: Centromeres are chromosomal loci necessary for chromosome segregation. The most common form of centromere is the regional centromere that is present once, and only once, per chromosome. Centromeres are epigenetically regulated; the centromere‐specific histone H3 variant CENP‐A is the determinant of centromere identity. Centromeres assemble kinetochores consisting of multiple copies of >100 proteins that regulate chromosome interactions with the mitotic spindle. Centromeres are flanked by heterochromatin, which is necessary for sister chromatid cohesion and error correction. Plasticity in centromere positioning and activity can compensate for the loss or gain of a centromere on a single chromosome fragment.

show abstract

Epigenetic engineering shows H3K4me2 is required for HJURP targeting and CENP-A assembly on a synthetic human kinetochore

Cited by 273 publications

References 62 publications

Pericentric and centromeric transcription: a perfect balance required

Pericentric and centromeric transcription: a perfect balance required

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

Centromeres

Contact Info

Product

Resources

About