The telomere bouquet regulates meiotic centromere assembly

Michael Klutstein; Alex Fennell; Alfonso Fernández-Álvarez; Julia Promisel Cooper

doi:10.1038/ncb3132

Centromere Protein B Null Mice are Mitotically and Meiotically Normal but Have Lower Body and Testis Weights

The Journal of Cell Biology ◽

10.1083/jcb.141.2.309 ◽

1998 ◽

Vol 141 (2) ◽

pp. 309-319 ◽

Cited By ~ 142

Author(s):

Damien F. Hudson ◽

Kerry J. Fowler ◽

Elizabeth Earle ◽

Richard Saffery ◽

Paul Kalitsis ◽

...

Keyword(s):

Cell Cycle Progression ◽

Mammalian Species ◽

Experimental Studies ◽

Conflicting Evidence ◽

Body Weights ◽

Reduced Rate ◽

And Function ◽

Centromere Assembly ◽

Mitosis And Meiosis

CENP-B is a constitutive centromere DNA-binding protein that is conserved in a number of mammalian species and in yeast. Despite this conservation, earlier cytological and indirect experimental studies have provided conflicting evidence concerning the role of this protein in mitosis. The requirement of this protein in meiosis has also not previously been described. To resolve these uncertainties, we used targeted disruption of the Cenpb gene in mouse to study the functional significance of this protein in mitosis and meiosis. Male and female Cenpb null mice have normal body weights at birth and at weaning, but these subsequently lag behind those of the heterozygous and wild-type animals. The weight and sperm content of the testes of Cenpb null mice are also significantly decreased. Otherwise, the animals appear developmentally and reproductively normal. Cytogenetic fluorescence-activated cell sorting and histological analyses of somatic and germline tissues revealed no abnormality. These results indicate that Cenpb is not essential for mitosis or meiosis, although the observed weight reduction raises the possibility that Cenpb deficiency may subtly affect some aspects of centromere assembly and function, and result in reduced rate of cell cycle progression, efficiency of microtubule capture, and/or chromosome movement. A model for a functional redundancy of this protein is presented.

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Considerations regarding centromere assembly in plant whole-genome sequencing

Methods ◽

10.1016/j.ymeth.2020.09.006 ◽

2020 ◽

Author(s):

Miaomiao Han ◽

Yae Yang ◽

Muqing Zhang ◽

Kai Wang

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome ◽

Centromere Assembly

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Centromere Targeting of the Chromosomal Passenger Complex Requires a Ternary Subcomplex of Borealin, Survivin, and the N-Terminal Domain of INCENP

Molecular Biology of the Cell ◽

10.1091/mbc.e05-12-1133 ◽

2006 ◽

Vol 17 (6) ◽

pp. 2547-2558 ◽

Cited By ~ 104

Author(s):

Ulf R. Klein ◽

Erich A. Nigg ◽

Ulrike Gruneberg

Keyword(s):

Functional Module ◽

Aurora B ◽

Serine Threonine Kinase ◽

Chromosomal Passenger Complex ◽

Chromosomal Passenger ◽

Core Components ◽

Interfering Rna ◽

Centromere Assembly

The chromosomal passenger complex (CPC), consisting of the serine/threonine kinase Aurora B, the inner centromere protein INCENP, Survivin, and Borealin/DasraB, has essential functions at the centromere in ensuring correct chromosome alignment and segregation. Despite observations that small interfering RNA-mediated knockdown of any one member of the CPC abolishes localization of the other subunits, it remains unclear how the complex is targeted to the centromere. We have now identified a ternary subcomplex of the CPC comprising Survivin, Borealin, and the N-terminal 58 amino acids of INCENP in vitro and in vivo. This subcomplex was found to be essential and sufficient for targeting to the centromere. Notably, Aurora B kinase, the enzymatic core of the CPC, was not required for centromere localization of the subcomplex. We demonstrate that CPC targeting to the centromere does not depend on CENP-A and hMis12, two core components for kinetochore/centromere assembly, and provide evidence that the CPC may be directed to centromeric DNA directly via the Borealin subunit. Our findings thus establish a functional module within the CPC that assembles on the N terminus of INCENP and controls centromere recruitment.

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Sequential de novo centromere formation and inactivation on a chromosomal fragment in maize

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1418248112 ◽

2015 ◽

Vol 112 (11) ◽

pp. E1263-E1271 ◽

Cited By ~ 26

Author(s):

Yalin Liu ◽

Handong Su ◽

Junling Pang ◽

Zhi Gao ◽

Xiu-Jie Wang ◽

...

Keyword(s):

Dna Sequences ◽

De Novo ◽

B Chromosome ◽

Chromosome 9 ◽

Centromeric Dna ◽

Repeat Sequences ◽

Centromeric Repeat ◽

And Function ◽

Centromere Assembly ◽

Derivatives Of

The ability of centromeres to alternate between active and inactive states indicates significant epigenetic aspects controlling centromere assembly and function. In maize (Zea mays), misdivision of the B chromosome centromere on a translocation with the short arm of chromosome 9 (TB-9Sb) can produce many variants with varying centromere sizes and centromeric DNA sequences. In such derivatives of TB-9Sb, we found a de novo centromere on chromosome derivative 3-3, which has no canonical centromeric repeat sequences. This centromere is derived from a 288-kb region on the short arm of chromosome 9, and is 19 megabases (Mb) removed from the translocation breakpoint of chromosome 9 in TB-9Sb. The functional B centromere in progenitor telo2-2 is deleted from derivative 3-3, but some B-repeat sequences remain. The de novo centromere of derivative 3-3 becomes inactive in three further derivatives with new centromeres being formed elsewhere on each chromosome. Our results suggest that de novo centromere initiation is quite common and can persist on chromosomal fragments without a canonical centromere. However, we hypothesize that when de novo centromeres are initiated in opposition to a larger normal centromere, they are cleared from the chromosome by inactivation, thus maintaining karyotype integrity.

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CENP-A drives asymmetric cell division and maintains stem identity

10.1101/631598 ◽

2019 ◽

Author(s):

Anna A. Dattoli ◽

Ben L. Carty ◽

Antje M. Kochendoerfer ◽

Annie E. Walshe ◽

Elaine M. Dunleavy

Keyword(s):

Stem Cell ◽

Asymmetric Cell Division ◽

Germline Stem Cells ◽

Cell Identity ◽

Over Expression ◽

Identity Maintenance ◽

Oocyte Meiosis ◽

Assembly Factor ◽

Female Germline ◽

Centromere Assembly

SUMMARYCentromeres, chromosomal loci essential for genome integrity, are epigenetically defined by CENP-A-containing chromatin. Recent studies suggest that parental CENP-A is asymmetrically distributed upon stem cell asymmetric division. However, a direct link between centromeres and stem cell identity has not been demonstrated. We show that Drosophila female germline stem cells (GSCs) and neuroblasts assemble centromeres between G2-phase and prophase, requiring CYCLIN A. Intriguingly, chromosomes that will be inherited by GSCs incorporate more CENP-A and capture more spindle fibers at pro-metaphase. Furthermore, over-expression of CAL1 (Drosophila CENP-A assembly factor) causes GSC-like tumours, while over-expression of both CENP-A and CAL1 promotes stem cell self-renewal. Finally, once centromeres have been assembled in GSCs, continued CENP-A assembly is not required in differentiating cells outside of the niche and CAL1 becomes dispensable. According to our results CENP-A regulates stem cell identity/maintenance. Moreover, crucial centromere assembly occurs in the niche prior to oocyte meiosis.

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CENP-C regulates centromere assembly, asymmetry and epigenetic age in Drosophila germline stem cells

10.1101/2020.11.02.364794 ◽

2020 ◽

Author(s):

Ben L Carty ◽

Anna A Dattoli ◽

Elaine M Dunleavy

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Fate ◽

Germ Line ◽

Asymmetric Distribution ◽

Germline Stem Cells ◽

Daughter Cells ◽

Sister Chromatids ◽

Asymmetric Divisions ◽

Centromere Assembly

AbstractGermline stem cells divide asymmetrically to produce one new daughter stem cell and one daughter cell that will subsequently undergo meiosis and differentiate to generate the mature gamete. The silent sister hypothesis proposes that in asymmetric divisions, the selective inheritance of sister chromatids carrying specific epigenetic marks between stem and daughter cells impacts cell fate. To facilitate this selective inheritance, the hypothesis specifically proposes that the centromeric region of each sister chromatid is distinct. In Drosophila germ line stem cells (GSCs), it has recently been shown that the centromeric histone CENP-A (called CID in flies) - the epigenetic determinant of centromere identity - is asymmetrically distributed between sister chromatids. In these cells, CID deposition occurs in G2 phase such that sister chromatids destined to end up in the stem cell harbour more CENP-A, assemble more kinetochore proteins and capture more spindle microtubules. These results suggest a potential mechanism of ‘mitotic drive’ that might bias chromosome segregation. Here we report that the inner kinetochore protein CENP-C, is required for the assembly of CID in G2 phase in GSCs. Moreover, CENP-C is required to maintain a normal asymmetric distribution of CID between stem and daughter cells. In addition, we find that CID is lost from centromeres in aged GSCs and that a reduction in CENP-C accelerates this loss. Finally, we show that CENP-C depletion in GSCs disrupts the balance of stem and daughter cells in the ovary, shifting GSCs toward a self-renewal tendency. Ultimately, we provide evidence that centromere assembly and maintenance via CENP-C is required to sustain asymmetric divisions in female Drosophila GSCs.

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