CENP-A-containing Nucleosomes: Easier Disassembly versus Exclusive Centromeric Localization

Silva, Natalia Conde e; Black, Ben E.; Sivolob, Andrei; Filipski, Jan; Cleveland, Don W.; Prunell, Ariel

doi:10.1016/j.jmb.2007.04.064

Cited by 126 publications

(134 citation statements)

References 64 publications

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“…In multicellular eukaryotes, heterochromatin condensation would help to stabilize CenH3 tetramers by preventing nucleosome turnover (42). Our detection of two distinct forms of Cse4 particles, one at centromeres and the other on chromosome arms, thus reconciles seemingly conflicting reports of left-handed CenH3 octamers produced in vitro (10)(11)(12)(13)(14) and of right-handed wrapping (6) and heterotypic CenH3 tetramers (8, 9) observed in vivo. …”

Section: Discussionsupporting

confidence: 76%

“…It has been previously shown that the Cse4 nucleosome wraps DNA in a right-handed orientation (6,7), consistent with in vivo observations of heterotypic tetrameric nucleosomes in Drosophila (8) and humans (9). However, several studies have shown that CenH3 nucleosomes are left-handed octamers in vitro (10)(11)(12)(13)(14).…”

supporting

confidence: 76%

“…Cse4 nucleosomes are also enriched at promoters of highly transcribed genes in strains that do not overproduce Cse4 (14,18) (Fig. S8C), suggesting that high turnover is a normal mechanism for evicting misincorporated CenH3 from chromosome arms (11) (Fig. 7E).…”

Section: Discussionmentioning

confidence: 99%

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Tripartite organization of centromeric chromatin in budding yeast

Krassovsky

Henikoff

2011

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

166

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The centromere is the genetic locus that organizes the proteinaceous kinetochore and is responsible for attachment of the chromosome to the spindle at mitosis and meiosis. In most eukaryotes, the centromere consists of highly repetitive DNA sequences that are occupied by nucleosomes containing the CenH3 histone variant, whereas in budding yeast, a ∼120-bp centromere DNA element (CDE) that is sufficient for centromere function is occupied by a single right-handed histone variant CenH3 (Cse4) nucleosome. However, these in vivo observations are inconsistent with in vitro evidence for left-handed octameric CenH3 nucleosomes. To help resolve these inconsistencies, we characterized yeast centromeric chromatin at single base-pair resolution. Intact particles containing both Cse4 and H2A are precisely protected from micrococcal nuclease over the entire CDE of all 16 yeast centromeres in both solubilized chromatin and the insoluble kinetochore. Small DNAbinding proteins protect CDEI and CDEIII and delimit the centromeric nucleosome to the ∼80-bp CDEII, only enough for a single DNA wrap. As expected for a tripartite organization of centromeric chromatin, loss of Cbf1 protein, which binds to CDEI, both reduces the size of the centromere-protected region and shifts its location toward CDEIII. Surprisingly, Cse4 overproduction caused genome-wide misincorporation of nonfunctional CenH3-containing nucleosomes that protect ∼135 base pairs and are preferentially enriched at sites of high nucleosome turnover. Our detection of two forms of CenH3 nucleosomes in the yeast genome, a singly wrapped particle at the functional centromere and octamer-sized particles on chromosome arms, reconcile seemingly conflicting in vivo and in vitro observations. Saccharomyces cerevisiae | chromatin immunoprecipitation | chromosome segregation

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Section: Discussionsupporting

confidence: 76%

supporting

confidence: 76%

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Tripartite organization of centromeric chromatin in budding yeast

Krassovsky

Henikoff

2011

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

166

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“…Unifying observations in several studies suggest that heparin binds the trypsin-sensitive solvent-phase tails of the core histones (26) and renders the nucleosomes more accessible to nucleases (27,28). Furthermore, heparin increases enhancer-promoter communication (29) by disassembling the chromatin structure (30,31).…”

mentioning

confidence: 99%

Heparin exerts a dual effect on murine lupus nephritis by enhancing enzymatic chromatin degradation and preventing chromatin binding in glomerular membranes

Hedberg¹,

Fismen²,

Fenton³

et al. 2011

Arthritis & Rheumatism

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Objective. Association of nucleosome-IgG immune complexes with glomerular basement membranes (GBMs) is an important event in the development of lupus nephritis. Preventing this binding and/or increasing nuclease sensitivity of nucleosomes may be viable strategies for the prevention of the disease. Theoretically, heparin may alter nucleosomal structure and increase sensitivity to proteinases and nucleases, and may also inhibit binding of nucleosomes and nucleosome-IgG complexes to basement membrane structures. The aim of this study was to investigate whether and eventually how heparin prevents murine lupus nephritis.Methods. Surface plasmon resonance was used to analyze if heparin inhibits binding of nucleosomes to laminin and collagen. The effect of heparin on nucleaseand proteinase-mediated degradation of nucleosomes was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and agarose gel electrophoresis. In vitro results were compared with analyses in vivo in heparin-treated (NZB ؋ NZW)F 1 mice. Anti-doublestranded DNA antibody production, deposition of nucleosome-IgG complexes in GBMs, and development of proteinuria were monitored, and circulating chromatin fragments were quantified using quantitative polymerase chain reaction.Results. In vitro studies demonstrated that heparin increased enzymatic degradation of nucleosomes and almost completely inhibited binding of nucleosomes to laminin and collagen. (NZB ؋ NZW)F 1 mice treated with heparin demonstrated delayed or no antibody production and higher variation of circulating chromatin levels compared with untreated control mice. This effect was accompanied by highly reduced nucleosomeIgG complexes in GBMs and delayed development of nephritis.Conclusion. Increasing the degradation of nucleosomes, reducing their immunogenicity, and preventing binding of nucleosome-IgG complexes in glomeruli together provide an alternative basis for the treatment of lupus nephritis.

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“…The amino-terminal 40 amino acids of CENP-A, the most divergent domain from histone H3, undergoes specific posttranslational modifications that are thought to influence CENP-A nucleosome structure and function, although their significance remains largely unclear (Zeitlin et al 2001;Kunitoku et al 2003;Bailey et al 2013;Boeckmann et al 2013). The most amino-terminal a helix in CENP-A (residues 48 -56) is three residues shorter than that observed in histone H3 (residues 45 -56), yet this small difference results in a loss of a DNA interaction that causes different entry/exit angles of DNA from the CENP-A nucleosome, protects less DNA in classic nucleosome micrococcal nuclease digestion assays, and most likely has a key influence of overall centromeric chromatin structure (Conde e Silva et al 2007;Panchenko et al 2011;Tachiwana et al 2011). In the histone fold domain of CENP-A, a two-residue insertion (R80 and G81) in a loop domain is exposed in the CENP-A nucleosome and influences CENP-A nucleosome stability (Sekulic et al 2010;Tachiwana et al 2011).…”

Section: Distinguishing Features Of Centromeric Chromatinmentioning

confidence: 99%

The Centromere: Epigenetic Control of Chromosome Segregation during Mitosis

Westhorpe

Straight

2014

Cold Spring Harb Perspect Biol

143

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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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CENP-A-containing Nucleosomes: Easier Disassembly versus Exclusive Centromeric Localization

Cited by 126 publications

References 64 publications

Tripartite organization of centromeric chromatin in budding yeast

Tripartite organization of centromeric chromatin in budding yeast

Heparin exerts a dual effect on murine lupus nephritis by enhancing enzymatic chromatin degradation and preventing chromatin binding in glomerular membranes

The Centromere: Epigenetic Control of Chromosome Segregation during Mitosis

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