CENP-C recruits M18BP1 to centromeres to promote CENP-A chromatin assembly

Moree, Ben; Meyer, Corey B.; Fuller, Colin J.; Straight, Aaron F.

doi:10.1083/jcb.201106079

Cited by 200 publications

(308 citation statements)

References 55 publications

Supporting

Mentioning

290

Contrasting

Order By: Relevance

“…The role of RNAPII in promoting CENP-A deposition also is implied in studies that show the association of CENP-A with centromeric transcripts (8,20) and the association of the chromatin remodeler FACT with CENP-A chromatin (18). Interestingly, CENP-C also has been implicated recently in the recruitment of Mis18-binding protein 1 and HJURP to the centromere (32). Our demonstration that inhibition of mitotic transcriptional activity results in the destabilization of CENP-C suggests that RNAPII transcription at kinetochore also may have an upstream role in CENP-A loading, via the stabilization of CENP-C binding.…”

Section: Discussionmentioning

confidence: 92%

Active transcription and essential role of RNA polymerase II at the centromere during mitosis

Chan

Marshall

Saffery

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

240

287

View full text Add to dashboard Cite

Transcription of the centromeric regions has been reported to occur in G1 and S phase in different species. Here, we investigate whether transcription also occurs and plays a functional role at the mammalian centromere during mitosis. We show the presence of actively transcribing RNA polymerase II (RNAPII) and its associated transcription factors, coupled with the production of centromere satellite transcripts at the mitotic kinetochore. Specific inhibition of RNAPII activity during mitosis leads to a decrease in centromeric α-satellite transcription and a concomitant increase in anaphase-lagging cells, with the lagging chromosomes showing reduced centromere protein C binding. These findings demonstrate an essential role of RNA-PII in the transcription of α-satellite DNA, binding of centromere protein C, and the proper functioning of the mitotic kinetochore.chromatin | noncoding RNA | epigenetics T he centromere is an essential chromosomal structure that mediates microtubule attachment during cell division to ensure correct chromosome segregation. Although centromere function is highly conserved, centromere DNA sequences show no evolutionary conservation. Instead, centromeric chromatin typically is filled with species-specific satellite DNA sequences that lack transcribed genes. The presence of functional ectopic centromeres (neocentromeres) at genomic regions devoid of classical satellite DNA repeats confirmed the epigenetic nature of centromere function (1).The centromere is organized into two broad domains characterized by distinct sets of epigenetic determinants. The centromere core domain comprises the centromere-specific histone H3 variant centromere protein A (CENP-A) that is essential for kinetochore formation, whereas the pericentric heterochromatin is vital for sister chromatid cohesion (for review, see ref.2). In yeast, pericentric outermost DNA repeats are transcribed and processed by RNAi machinery into siRNAs, which direct the deposition of heterochromatic markers such as H3K9me3 and HP1 at the pericentric heterochromatin (3). The RNAi pathway also has been shown to be vital for the establishment of pericentric heterochromatin in plant and animal cells (4, 5). However, although the depletion of Dicer in human-chicken hybrid cells causes defective pericentric heterochromatin, it does not affect the binding of CENP-A and centromere protein C (CENP-C) at the centromere core domain (6), suggesting that the RNAi pathway is not required for core centromere function. Our previous studies showed that transcription is permissible within the kinetochore domain of a human neocentromere (7, 8), but others have reported the presence of active genes within the rice kinetochore domain (9). Consistent with these reports, the CENP-A domain in Drosophila and human cells is enriched with the euchromatin-like marker H3K4me2 (10). Such studies suggest that transcription of centromeric chromatin is permissible and compatible with centromere function. Furthermore, we and others have demonstrated the presence of RNA at th...

show abstract

Section: Discussionmentioning

confidence: 92%

Active transcription and essential role of RNA polymerase II at the centromere during mitosis

Chan

Marshall

Saffery

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

240

287

View full text Add to dashboard Cite

show abstract

“…Thus, CENP-C is essential for the assembly of new CENP-A, as previously suggested. 33 In contrast, depletion of CENP-T to less than 10% of its normal levels in the extract does not have a major effect on CENP-A deposition (Fig. 4A and 4D).…”

Section: Cenp-t and Cenp-w Are Not Required For Cenp-a Depositionmentioning

confidence: 93%

“…30,31 The contribution of CENP-N to the CENP-A deposition pathway is unknown whereas CENP-C has been proposed to drive HJURP targeting to centromeres through the Mis18 complex. 33,34 CENP-T and CENP-W do not bind CENP-A but instead recognize H3 nucleosomes present in centromeric chromatin. 35,36 These two proteins together with CENP-S and CENP-X, all 4 containing histone-fold domains, have been proposed to form a nucleosome-like particle capable of supercoiling DNA in vitro.…”

Section: Introductionmentioning

confidence: 99%

The distinct functions of CENP-C and CENP-T/W in centromere propagation and function inXenopusegg extracts

Krizaic

Williams

Sánchez

et al. 2015

Nucleus

View full text Add to dashboard Cite

“…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%

“…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. Together with the early localization of the Mis18 complex to centromeres, these data have led to suggestions that the Mis18 complex is a key player in CENP-A assembly process.…”

Section: The Mis18 Complexmentioning

confidence: 99%

The Centromere: Epigenetic Control of Chromosome Segregation during Mitosis

Westhorpe

Straight

2014

Cold Spring Harb Perspect Biol

Self Cite

147

View full text Add to dashboard Cite

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.

show abstract

CENP-C recruits M18BP1 to centromeres to promote CENP-A chromatin assembly

Abstract: CENP-C provides a link between existing CENP-A chromatin and the proteins required for new CENP-A nucleosome assembly.

Cited by 200 publications

References 55 publications

Active transcription and essential role of RNA polymerase II at the centromere during mitosis

Active transcription and essential role of RNA polymerase II at the centromere during mitosis

The distinct functions of CENP-C and CENP-T/W in centromere propagation and function inXenopusegg extracts

The Centromere: Epigenetic Control of Chromosome Segregation during Mitosis

Contact Info

Product

Resources

About