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https://www.readbyqxmd.com/read/28094382/the-supercoiling-state-of-dna-determines-the-handedness-of-both-h3-and-cenp-a-nucleosomes
#1
R Vlijm, S H Kim, P L De Zwart, Y Dalal, C Dekker
Nucleosomes form the unit structure of the genome in eukaryotes, thereby constituting a fundamental tenet of chromatin biology. In canonical nucleosomes, DNA wraps around the histone octamer in a left-handed toroidal ramp. Here, in single-molecule magnetic tweezers studies of chaperone-assisted nucleosome assembly, we show that the handedness of the DNA wrapping around the nucleosome core is intrinsically ambidextrous, and depends on the pre-assembly supercoiling state of the DNA, i.e., it is not uniquely determined by the octameric histone core...
January 17, 2017: Nanoscale
https://www.readbyqxmd.com/read/28073008/cenp-a-modifications-on-ser68-and-lys124-are-dispensable-for-establishment-maintenance-and-long-term-function-of-human-centromeres
#2
Daniele Fachinetti, Glennis A Logsdon, Amira Abdullah, Evan B Selzer, Don W Cleveland, Ben E Black
CENP-A is a histone H3 variant key to epigenetic specification of mammalian centromeres. Using transient overexpression of CENP-A mutants, two recent reports in Developmental Cell proposed essential centromere functions for post-translational modifications of human CENP-A. Phosphorylation at Ser68 was proposed to have an essential role in CENP-A deposition at centromeres. Blockage of ubiquitination at Lys124 was proposed to abrogate localization of CENP-A to the centromere. Following gene inactivation and replacement in human cells, we demonstrate that CENP-A mutants that cannot be phosphorylated at Ser68 or ubiquitinated at Lys124 assemble efficiently at centromeres during G1, mediate early events in centromere establishment at an ectopic chromosomal locus, and maintain centromere function indefinitely...
January 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28069312/centromeres-drive-a-hard-bargain
#3
REVIEW
Leah F Rosin, Barbara G Mellone
Centromeres are essential chromosomal structures that mediate the accurate distribution of genetic material during meiotic and mitotic cell divisions. In most organisms, centromeres are epigenetically specified and propagated by nucleosomes containing the centromere-specific H3 variant, centromere protein A (CENP-A). Although centromeres perform a critical and conserved function, CENP-A and the underlying centromeric DNA are rapidly evolving. This paradox has been explained by the centromere drive hypothesis, which proposes that CENP-A is undergoing an evolutionary tug-of-war with selfish centromeric DNA...
January 6, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28059702/cdk-regulated-dimerization-of-m18bp1-on-a-mis18-hexamer-is-necessary-for-cenp-a-loading
#4
Dongqing Pan, Kerstin Klare, Arsen Petrovic, Annika Take, Kai Walstein, Priyanka Singh, Arnaud Rondelet, Alexander W Bird, Andrea Musacchio
Centromeres are unique chromosomal loci that promote the assembly of kinetochores, macromolecular complexes that bind spindle microtubules during mitosis. In most organisms, centromeres lack defined genetic features. Rather, they are specified epigenetically by a centromere-specific histone H3 variant, CENP-A. The Mis18 complex, comprising the Mis18α:Mis18β subcomplex and M18BP1, is crucial for CENP-A homeostasis. It recruits the CENP-A-specific chaperone HJURP to centromeres and primes it for CENP-A loading...
January 6, 2017: ELife
https://www.readbyqxmd.com/read/28017591/a-dual-inhibitory-mechanism-sufficient-to-maintain-cell-cycle-restricted-cenp-a-assembly
#5
Ana Stankovic, Lucie Y Guo, João F Mata, Dani L Bodor, Xing-Jun Cao, Aaron O Bailey, Jeffrey Shabanowitz, Donald F Hunt, Benjamin A Garcia, Ben E Black, Lars E T Jansen
Chromatin featuring the H3 variant CENP-A at the centromere is critical for its mitotic function and epigenetic maintenance. Assembly of centromeric chromatin is restricted to G1 phase through inhibitory action of Cdk1/2 kinases in other phases of the cell cycle. Here, we identify the two key targets sufficient to maintain cell-cycle control of CENP-A assembly. We uncovered a single phosphorylation site in the licensing factor M18BP1 and a cyclin A binding site in the CENP-A chaperone, HJURP, that mediated specific inhibitory phosphorylation...
January 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/27940888/constitutive-centromere-associated-network-controls-centromere-drift-in-vertebrate-cells
#6
Tetsuya Hori, Naoko Kagawa, Atsushi Toyoda, Asao Fujiyama, Sadahiko Misu, Norikazu Monma, Fumiaki Makino, Kazuho Ikeo, Tatsuo Fukagawa
Centromeres are specified by sequence-independent epigenetic mechanisms, and the centromere position may drift at each cell cycle, but once this position is specified, it may not be frequently moved. Currently, it is unclear whether the centromere position is stable. To address this question, we systematically analyzed the position of nonrepetitive centromeres in 21 independent clones isolated from a laboratory stock of chicken DT40 cells using chromatin immunoprecipitation combined with massive parallel sequencing analysis with anti-CENP-A antibody...
January 2, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/27918550/selective-y-centromere-inactivation-triggers-chromosome-shattering-in-micronuclei-and-repair-by-non-homologous-end-joining
#7
Peter Ly, Levi S Teitz, Dong H Kim, Ofer Shoshani, Helen Skaletsky, Daniele Fachinetti, David C Page, Don W Cleveland
Chromosome missegregation into a micronucleus can cause complex and localized genomic rearrangements known as chromothripsis, but the underlying mechanisms remain unresolved. Here we developed an inducible Y centromere-selective inactivation strategy by exploiting a CENP-A/histone H3 chimaera to directly examine the fate of missegregated chromosomes in otherwise diploid human cells. Using this approach, we identified a temporal cascade of events that are initiated following centromere inactivation involving chromosome missegregation, fragmentation, and re-ligation that span three consecutive cell cycles...
January 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/27911702/the-unconventional-kinetoplastid-kinetochore-from-discovery-toward-functional-understanding
#8
REVIEW
Bungo Akiyoshi
The kinetochore is the macromolecular protein complex that drives chromosome segregation in eukaryotes. Its most fundamental function is to connect centromeric DNA to dynamic spindle microtubules. Studies in popular model eukaryotes have shown that centromere protein (CENP)-A is critical for DNA-binding, whereas the Ndc80 complex is essential for microtubule-binding. Given their conservation in diverse eukaryotes, it was widely believed that all eukaryotes would utilize these components to make up a core of the kinetochore...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27893298/replication-checkpoint-suppression-and-structure-of-centromeric-dna
#9
Francesco Romeo, Lucia Falbo, Vincenzo Costanzo
Human centromeres contain large amounts of repetitive DNA sequences known as α satellite DNA, which can be difficult to replicate and whose functional role is unclear. Recently, we have characterized protein composition, structural organization and checkpoint response to stalled replication forks of centromeric chromatin reconstituted in Xenopus laevis egg extract. We showed that centromeric DNA has high affinity for SMC2-4 subunits of condensins and for CENP-A, it is enriched for DNA repair factors and suppresses the ATR checkpoint to ensure its efficient replication...
November 2016: Nucleus
https://www.readbyqxmd.com/read/27880912/cenp-a-is-dispensable-for-mitotic-centromere-function-after-initial-centromere-kinetochore-assembly
#10
Sebastian Hoffmann, Marie Dumont, Viviana Barra, Peter Ly, Yael Nechemia-Arbely, Moira A McMahon, Solène Hervé, Don W Cleveland, Daniele Fachinetti
Human centromeres are defined by chromatin containing the histone H3 variant CENP-A assembled onto repetitive alphoid DNA sequences. By inducing rapid, complete degradation of endogenous CENP-A, we now demonstrate that once the first steps of centromere assembly have been completed in G1/S, continued CENP-A binding is not required for maintaining kinetochore attachment to centromeres or for centromere function in the next mitosis. Degradation of CENP-A prior to kinetochore assembly is found to block deposition of CENP-C and CENP-N, but not CENP-T, thereby producing defective kinetochores and failure of chromosome segregation...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27858158/structure-of-centromere-chromatin-from-nucleosome-to-chromosomal-architecture
#11
REVIEW
Thomas Schalch, Florian A Steiner
The centromere is essential for the segregation of chromosomes, as it serves as attachment site for microtubules to mediate chromosome segregation during mitosis and meiosis. In most organisms, the centromere is restricted to one chromosomal region that appears as primary constriction on the condensed chromosome and is partitioned into two chromatin domains: The centromere core is characterized by the centromere-specific histone H3 variant CENP-A (also called cenH3) and is required for specifying the centromere and for building the kinetochore complex during mitosis...
November 17, 2016: Chromosoma
https://www.readbyqxmd.com/read/27820823/cenp-a-and-h3-nucleosomes-display-a-similar-stability-to-force-mediated-disassembly
#12
Sung Hyun Kim, Rifka Vlijm, Jaco van der Torre, Yamini Dalal, Cees Dekker
Centromere-specific nucleosomes are a central feature of the kinetochore complex during mitosis, in which microtubules exert pulling and pushing forces upon the centromere. CENP-A nucleosomes have been assumed to be structurally unique, thereby providing resilience under tension relative to their H3 canonical counterparts. Here, we directly test this hypothesis by subjecting CENP-A and H3 octameric nucleosomes, assembled on random or on centromeric DNA sequences, to varying amounts of applied force by using single-molecule magnetic tweezers...
2016: PloS One
https://www.readbyqxmd.com/read/27811920/acetylation-of-histone-h4-lysine-5-and-12-is-required-for-cenp-a-deposition-into-centromeres
#13
Wei-Hao Shang, Tetsuya Hori, Frederick G Westhorpe, Kristina M Godek, Atsushi Toyoda, Sadahiko Misu, Norikazu Monma, Kazuho Ikeo, Christopher W Carroll, Yasunari Takami, Asao Fujiyama, Hiroshi Kimura, Aaron F Straight, Tatsuo Fukagawa
Centromeres are specified epigenetically through the deposition of the centromere-specific histone H3 variant CENP-A. However, how additional epigenetic features are involved in centromere specification is unknown. Here, we find that histone H4 Lys5 and Lys12 acetylation (H4K5ac and H4K12ac) primarily occur within the pre-nucleosomal CENP-A-H4-HJURP (CENP-A chaperone) complex, before centromere deposition. We show that H4K5ac and H4K12ac are mediated by the RbAp46/48-Hat1 complex and that RbAp48-deficient DT40 cells fail to recruit HJURP to centromeres and do not incorporate new CENP-A at centromeres...
November 4, 2016: Nature Communications
https://www.readbyqxmd.com/read/27807043/hjurp-interaction-with-the-condensin-ii-complex-during-g1-promotes-cenp-a-deposition
#14
Meghan C Barnhart-Dailey, Prasad Trivedi, P Todd Stukenberg, Daniel R Foltz
Centromeric chromatin is required for kinetochore assembly during mitosis and accurate chromosome segregation. A unique nucleosome containing the histone H3-specific variant CENP-A is the defining feature of centromeric chromatin. In humans, CENP-A nucleosome deposition occurs in early G1 just after mitotic exit at the time when the CENP-A deposition machinery localizes to centromeres. The mechanism by which CENP-A is deposited onto an existing, condensed chromatin template is not understood. Here we identify the selective association of the CENP-A chaperone HJURP with the condensin II complex and not condensin I...
January 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27794026/histone-h4-facilitates-the-proteolysis-of-the-budding-yeast-cenp-acse4-centromeric-histone-variant
#15
Gary M R Deyter, Erica M Hildebrand, Adrienne D Barber, Sue Biggins
The incorporation of histone variants into nucleosomes can alter chromatin-based processes. CENP-A is the histone H3 variant found exclusively at centromeres that serves as an epigenetic mark for centromere identity and is required for kinetochore assembly. CENP-A mislocalization to ectopic sites appears to contribute to genomic instability, transcriptional misregulation, and tumorigenesis, so mechanisms exist to ensure its exclusive localization to centromeres. One conserved process is proteolysis, which is mediated by the Psh1 E3 ubiquitin ligase in Saccharomyces cerevisiae (budding yeast)...
January 2017: Genetics
https://www.readbyqxmd.com/read/27716277/array-cgh-diagnosis-in-ovarian-failure-identification-of-new-molecular-actors-for-ovarian-physiology
#16
Sylvie Jaillard, Linda Akloul, Marion Beaumont, Houda Hamdi-Roze, Christele Dubourg, Sylvie Odent, Solène Duros, Nathalie Dejucq-Rainsford, Marc-Antoine Belaud-Rotureau, Célia Ravel
BACKGROUND: Ovarian failure (OF) is considered premature if it occurs before the age of 40. This study investigates the genetic aetiology underlying OF in women under the age of 40 years. METHODS: We conducted an experimental prospective study performing all genome microarrays in 60 patients younger than 40 years presenting an OF revealed by a decrease of circulating Anti-Müllerian Hormone (AMH) and leading to an oocyte donation program. RESULTS: We identified nine significant copy number variations (CNVs) including candidate genes potentially implicated in reproductive function...
October 3, 2016: Journal of Ovarian Research
https://www.readbyqxmd.com/read/27696824/maintenance-and-function-of-a-plant-chromosome-in-human-cells
#17
Naoki Wada, Yasuhiro Kazuki, Kanako Kazuki, Toshiaki Inoue, Kiichi Fukui, Mitsuo Oshimura
Replication, segregation, gene expression and inheritance are essential features of all eukaryotic chromosomes. To delineate the extent of conservation of chromosome functions between humans and plants during evolutionary history, we have generated the first human cell line containing an Arabidopsis chromosome. The Arabidopsis chromosome was mitotically stable in hybrid cells following cell division, and initially existed as a translocated chromosome. During culture, the translocated chromosomes then converted to two types of independent plant chromosomes without human DNA sequences, with the reproducibility...
October 4, 2016: ACS Synthetic Biology
https://www.readbyqxmd.com/read/27670610/skin-specific-deletion-of-mis18%C3%AE-impedes-proliferation-and-stratification-of-epidermal-keratinocytes
#18
Koog Chan Park, Minkyoung Lee, Yoon Jeon, Raok Jeon, Sung Hee Baek, Ho Lee, Keun Il Kim
The Mis18 proteins (Mis18α, Mis18β and M18BP1) are pivotal to the deposition of CENP-A at the centromere during cell cycle progression and are indispensable for embryonic development. Here, we show that Mis18α is critical for the proliferation of keratinocytes and stratification of the epidermis. Mice lacking Mis18α in the epidermis died shortly after birth, showing skin abnormalities like thin and translucent skin as well as defective skin barrier functions. The epidermis of newborn Mis18α-deficient mice lacked distinct stratification and mature hair follicles, with a reduction in the number of proliferating cells and increased cell death in the basal layer...
September 23, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27666591/ccp1-homodimer-mediates-chromatin-integrity-by-antagonizing-cenp-a-loading
#19
Qianhua Dong, Feng-Xiang Yin, Feng Gao, Yuan Shen, Faben Zhang, Yang Li, Haijin He, Marlyn Gonzalez, Jinpu Yang, Shu Zhang, Min Su, Yu-Hang Chen, Fei Li
CENP-A is a centromere-specific histone 3 variant essential for centromere specification. CENP-A partially replaces canonical histone H3 at the centromeres. How the particular CENP-A/H3 ratio at centromeres is precisely maintained is unknown. It also remains unclear how CENP-A is excluded from non-centromeric chromatin. Here, we identify Ccp1, an uncharacterized NAP family protein in fission yeast that antagonizes CENP-A loading at both centromeric and non-centromeric regions. Like the CENP-A loading factor HJURP, Ccp1 interacts with CENP-A and is recruited to centromeres at the end of mitosis in a Mis16-dependent manner...
October 6, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27652331/the-inheritance-of-centromere-identity
#20
Yohei Niikura, Risa Kitagawa, Katsumi Kitagawa
CENP-A (Centromere protein A) is a histone H3 variant that epigenetically determines the centromere position, but the mechanism of its centromere inheritance is obscure. We propose that CENP-A ubiquitylation, which is inherited through dimerization between rounds of cell division, is a candidate for the epigenetic mark of centromere identity.
July 2016: Molecular & Cellular Oncology
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