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https://www.readbyqxmd.com/read/29212814/structural-basis-for-assembly-of-the-cbf3-kinetochore-complex
#1
Vera Leber, Andrea Nans, Martin R Singleton
Eukaryotic chromosomes contain a specialised region known as the centromere, which forms the platform for kinetochore assembly and microtubule attachment. The centromere is distinguished by the presence of nucleosomes containing the histone H3 variant, CENP-A. In budding yeast, centromere establishment begins with the recognition of a specific DNA sequence by the CBF3 complex. This in turn facilitates CENP-ACse4 nucleosome deposition and kinetochore assembly. Here, we describe a 3.6 Å single-particle cryo-EM reconstruction of the core CBF3 complex, incorporating the sequence-specific DNA-binding protein Cep3 together with regulatory subunits Ctf13 and Skp1...
December 6, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29208640/shaping-chromatin-in-the-nucleus-the-bricks-and-the-architects
#2
David Sitbon, Katrina Podsypanina, Tejas Yadav, Geneviève Almouzni
Chromatin organization in the nucleus provides a vast repertoire of information in addition to that encoded genetically. Understanding how this organization impacts genome stability and influences cell fate and tumorigenesis is an area of rapid progress. Considering the nucleosome, the fundamental unit of chromatin structure, the study of histone variants (the bricks) and their selective loading by histone chaperones (the architects) is particularly informative. Here, we report recent advances in understanding how relationships between histone variants and their chaperones contribute to tumorigenesis using cell lines and Xenopus development as model systems...
December 5, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/29196559/remarkable-evolutionary-plasticity-of-centromeric-chromatin
#3
Steven Henikoff, Jitendra Thakur, Sivakanthan Kasinathan, Paul B Talbert
Centromeres were familiar to cell biologists in the late 19th century, but for most eukaryotes the basis for centromere specification has remained enigmatic. Much attention has been focused on the cenH3 (CENP-A) histone variant, which forms the foundation of the centromere. To investigate the DNA sequence requirements for centromere specification, we applied a variety of epigenomic approaches, which have revealed surprising diversity in centromeric chromatin properties. Whereas each point centromere of budding yeast is occupied by a single precisely positioned tetrameric nucleosome with one cenH3 molecule, the "regional" centromeres of fission yeast contain unphased presumably octameric nucleosomes with two cenH3s...
December 1, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/29194511/prolyl-isomerization-of-the-cenp-a-n-terminus-regulates-centromeric-integrity-in-fission-yeast
#4
Hwei Ling Tan, Kim Kiat Lim, Qiaoyun Yang, Jing-Song Fan, Ahmed Mahmoud Mohammed Sayed, Liy Sim Low, Bingbing Ren, Teck Kwang Lim, Qingsong Lin, Yu-Keung Mok, Yih-Cherng Liou, Ee Sin Chen
Centromeric identity and chromosome segregation are determined by the precise centromeric targeting of CENP-A, the centromere-specific histone H3 variant. The significance of the amino-terminal domain (NTD) of CENP-A in this process remains unclear. Here, we assessed the functional significance of each residue within the NTD of CENP-A from Schizosaccharomyces pombe (SpCENP-A) and identified a proline-rich 'GRANT' (Genomic stability-Regulating site within CENP-A N-Terminus) motif that is important for CENP-A function...
November 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29180432/phosphorylation-of-cenp-c-by-aurora-b-facilitates-kinetochore-attachment-error-correction-in-mitosis
#5
Xing Zhou, Fan Zheng, Chengliang Wang, Minhao Wu, Xiaozhen Zhang, Qian Wang, Xuebiao Yao, Chuanhai Fu, Xuan Zhang, Jianye Zang
Kinetochores are superprotein complexes that orchestrate chromosome segregation via a dynamic interaction with spindle microtubules. A physical connection between CENP-C and the Mis12-Ndc80-Knl1 (KMN) protein network is an important pathway that is used to assemble kinetochores on CENP-A nucleosomes. Multiple outer kinetochore components are phosphorylated by Aurora B kinase to activate the spindle assembly checkpoint (SAC) and to ensure accurate chromosome segregation. However, it is unknown whether Aurora B can phosphorylate inner kinetochore components to facilitate proper mitotic chromosome segregation...
November 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29119119/an-exploration-of-the-impact-of-anticentromere-antibody-on-early-stage-embryo
#6
Ying Ying, Xi Guo, Yiping Zhong, Canquan Zhou
Background: Previously, we found women with positive anticentromere antibody showed impaired potential of oocyte maturation and embryo cleavage; the possible mechanism behind this phenomenon was still unknown. Objective: Thus, the present study aimed to preliminarily explore whether ACA could penetrate into the living embryos and impair their developmental potential via in vitro coculture with mouse embryos. Methods: Mouse embryos were collected and used for in vitro culture with polyclonal anticentromere protein A (CENP-A) antibody; then, immunofluorescence assay was performed to determine the penetration of antibody into embryos, and embryo development potential was observed...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29074736/molecular-basis-of-cenp-c-association-with-the-cenp-a-nucleosome-at-yeast-centromeres
#7
Hua Xiao, Feng Wang, Jan Wisniewski, Alexey K Shaytan, Rodolfo Ghirlando, Peter C FitzGerald, Yingzi Huang, Debbie Wei, Shipeng Li, David Landsman, Anna R Panchenko, Carl Wu
Histone CENP-A-containing nucleosomes play an important role in nucleating kinetochores at centromeres for chromosome segregation. However, the molecular mechanisms by which CENP-A nucleosomes engage with kinetochore proteins are not well understood. Here, we report the finding of a new function for the budding yeast Cse4/CENP-A histone-fold domain interacting with inner kinetochore protein Mif2/CENP-C. Strikingly, we also discovered that AT-rich centromere DNA has an important role for Mif2 recruitment. Mif2 contacts one side of the nucleosome dyad, engaging with both Cse4 residues and AT-rich nucleosomal DNA...
October 26, 2017: Genes & Development
https://www.readbyqxmd.com/read/29040671/nanoscale-dynamics-of-centromere-nucleosomes-and-the-critical-roles-of-cenp-a
#8
Micah P Stumme-Diers, Siddhartha Banerjee, Mohtadin Hashemi, Zhiqiang Sun, Yuri L Lyubchenko
In the absence of a functioning centromere, chromosome segregation becomes aberrant, leading to an increased rate of aneuploidy. The highly specific recognition of centromeres by kinetochores suggests that specific structural characteristics define this region, however, the structural details and mechanism underlying this recognition remains a matter of intense investigation. To address this, high-speed atomic force microscopy was used for direct visualization of the spontaneous dynamics of CENP-A nucleosomes at the sub-second time scale...
October 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28980868/exploring-the-role-of-cenp-a-ser18-phosphorylation-in-cin-and-tumorigenesis
#9
Weiguo Zhang, Gary H Karpen, Qing Zhang
No abstract text is available yet for this article.
October 5, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28980861/budding-yeast-cenp-a-cse4-interacts-with-the-n-terminus-of-sgo1-and-regulates-its-association-with-centromeric-chromatin
#10
Prashant K Mishra, Kriti S Thapa, Panyue Chen, Suyu Wang, Tony R Hazbun, Munira A Basrai
Shugoshin is an evolutionarily conserved protein, which is involved in tension sensing on mitotic chromosomes, kinetochore biorientation, and protection of centromeric (CEN) cohesin for faithful chromosome segregation. Interaction of the C-terminus of Sgo1 with phosphorylated histone H2A regulates its association with CEN and pericentromeric (peri-CEN) chromatin, whereas mutations in histone H3 selectively compromise the association of Sgo1 with peri-CEN but not CEN chromatin. Given that histone H3 is absent from CEN and is replaced by a histone H3 variant CENP-A(Cse4), we investigated if CENP-A(Cse4) interacts with Sgo1 and promotes its association with the CEN chromatin...
October 5, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28916652/lsd1-mediated-epigenetic-reprogramming-drives-cenpe-expression-and-prostate-cancer-progression
#11
Yi Liang, Musaddeque Ahmed, Haiyang Guo, Fraser Soares, Junjie T Hua, Shuai Gao, Catherine Lu, Christine Poon, Wanting Han, Jens Langstein, Muhammad B Ekram, Brian Li, Elai Davicioni, Mandeep Takhar, Nicholas Erho, R Jeffrey Karnes, Dianne Chadwick, Theodorus van der Kwast, Paul C Boutros, Cheryl H Arrowsmith, Felix Y Feng, Anthony M Joshua, Amina Zoubeidi, Changmeng Cai, Housheng H He
Androgen receptor (AR) signaling is a key driver of prostate cancer, and androgen-deprivation therapy (ADT) is a standard treatment for patients with advanced and metastatic disease. However, patients receiving ADT eventually develop incurable castration-resistant prostate cancer (CRPC). Here, we report that the chromatin modifier LSD1, an important regulator of AR transcriptional activity, undergoes epigenetic reprogramming in CRPC. LSD1 reprogramming in this setting activated a subset of cell-cycle genes, including CENPE, a centromere binding protein and mitotic kinesin...
October 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28904333/the-ino80-complex-mediates-epigenetic-centromere-propagation-via-active-removal-of-histone-h3
#12
Eun Shik Choi, Youngseo Cheon, Keunsoo Kang, Daeyoup Lee
The centromere is the chromosomal locus at which the kinetochore is assembled to direct chromosome segregation. The histone H3 variant, centromere protein A (CENP-A), is known to epigenetically mark active centromeres, but the mechanism by which CENP-A propagates at the centromere, replacing histone H3, remains poorly understood. Using fission yeast, here we show that the Ino80 adenosine triphosphate (ATP)-dependent chromatin-remodeling complex, which removes histone H3-containing nucleosomes from associated chromatin, promotes CENP-A(Cnp1) chromatin assembly at the centromere in a redundant manner with another chromatin-remodeling factor Chd1(Hrp1)...
September 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28840245/centromere-dynamics-in-male-and-female-germ-cells
#13
Elaine M Dunleavy, Caitríona M Collins
In sexually reproducing organisms the germ line is the cellular lineage that gives rise to gametes. All germ cells originate from germline stem cells that divide asymmetrically to generate gonial pre-cursors, which are amplified in number by mitotic divisions, undergo meiosis and eventually differentiate into mature gametes (haploid eggs and sperm). Information transmitted with gametes is inherited by offspring, and potentially by subsequent generations, instructing in organismal development and beyond. Meiosis comprises one round of DNA replication, followed by two rounds of chromosome segregation; homologous chromosomes segregate in the first division (meiosis I) and sister chromatids segregate in the second division (meiosis II)...
2017: Progress in Molecular and Subcellular Biology
https://www.readbyqxmd.com/read/28840243/dna-sequences-in-centromere-formation-and-function
#14
M Dumont, D Fachinetti
Faithful chromosome segregation during cell division depends on the centromere, a complex DNA/protein structure that links chromosomes to spindle microtubules. This chromosomal domain has to be marked throughout cell division and its chromosomal localization preserved across cell generations. From fission yeast to human, centromeres are established on a series of repetitive DNA sequences and on specialized centromeric chromatin. This chromatin is enriched with the histone H3 variant, named CENP-A, that was demonstrated to be the epigenetic mark that maintains centromere identity and function indefinitely...
2017: Progress in Molecular and Subcellular Biology
https://www.readbyqxmd.com/read/28840239/post-translational-modifications-of-centromeric-chromatin
#15
Ana García Del Arco, Sylvia Erhardt
Regulation of chromatin structures is important for the control of DNA processes such as gene expression, and misregulation of chromatin is implicated in diverse diseases. Covalent post-translational modifications of histones are a prominent way to regulate chromatin structure and different chromatin regions bear their specific signature of histone modifications. The composition of centromeric chromatin is significantly different from other chromatin structures and mainly defined by the presence of the histone H3-variant CENP-A...
2017: Progress in Molecular and Subcellular Biology
https://www.readbyqxmd.com/read/28840238/artificial-chromosomes-and-strategies-to-initiate-epigenetic-centromere-establishment
#16
Evelyne J Barrey, Patrick Heun
In recent years, various synthetic approaches have been developed to address the question of what directs centromere establishment and maintenance. In this chapter, we will discuss how approaches aimed at constructing synthetic centromeres have co-evolved with and contributed to shape the theory describing the determinants of centromere identity. We will first review lessons learned from artificial chromosomes created from "naked" centromeric sequences to investigate the role of the underlying DNA for centromere formation...
2017: Progress in Molecular and Subcellular Biology
https://www.readbyqxmd.com/read/28840237/orchestrating-the-specific-assembly-of-centromeric-nucleosomes
#17
Ewelina Zasadzińska, Daniel R Foltz
Centromeres are chromosomal loci that are defined epigenetically in most eukaryotes by incorporation of a centromere-specific nucleosome in which the canonical histone H3 variant is replaced by Centromere Protein A (CENP-A). Therefore, the assembly and propagation of centromeric nucleosomes are critical for maintaining centromere identify and ensuring genomic stability. Centromeres direct chromosome segregation (during mitosis and meiosis) by recruiting the constitutive centromere-associated network of proteins throughout the cell cycle that in turn recruits the kinetochore during mitosis...
2017: Progress in Molecular and Subcellular Biology
https://www.readbyqxmd.com/read/28840236/quantitative-microscopy-reveals-centromeric-chromatin-stability-size-and-cell-cycle-mechanisms-to-maintain-centromere-homeostasis
#18
Ana Stankovic, Lars E T Jansen
Centromeres are chromatin domains specified by nucleosomes containing the histone H3 variant, CENP-A. This unique centromeric structure is at the heart of a strong self-templating epigenetic mechanism that renders centromeres heritable. We review how specific quantitative microscopy approaches have contributed to the determination of the copy number, architecture, size, and dynamics of centromeric chromatin and its associated centromere complex and kinetochore. These efforts revealed that the key to long-term centromere maintenance is the slow turnover of CENP-A nucleosomes, a critical size of the chromatin domain and its cell cycle-coupled replication...
2017: Progress in Molecular and Subcellular Biology
https://www.readbyqxmd.com/read/28827290/kinetochore-components-required-for-centromeric-chromatin-assembly-are-impacted-by-msc1-in-schizosaccharomyces-pombe
#19
Chenchao Gao, Lauren Langbein, Fariha Kamal, Anuja A George, Nancy C Walworth
Eukaryotic chromosome segregation requires a protein complex known as the kinetochore that mediates attachment between mitotic spindle microtubules and centromere-specific nucleosomes composed of the widely conserved histone variant CENP-A. Mutations in kinetochore proteins of the fission yeast Schizosaccharomyces pombe lead to chromosome missegregation such that daughter cells emerge from mitosis with unequal DNA content. We find that multiple copies of Msc1-a fission yeast homolog of the KDM5 family of proteins-suppresses the temperature-sensitive growth defect of several kinetochore mutants, including mis16 and mis18, as well as mis6, mis15, and mis17, components of the Constitutive Centromere Associated Network (CCAN)...
October 2017: Genetics
https://www.readbyqxmd.com/read/28819432/silencing-of-hjurp-induces-dysregulation-of-cell-cycle-and-ros-metabolism-in-bladder-cancer-cells-via-ppar%C3%AE-sirt1-feedback-loop
#20
Rui Cao, Gang Wang, Kaiyu Qian, Liang Chen, Guofeng Qian, Conghua Xie, Han C Dan, Wei Jiang, Min Wu, Chin-Lee Wu, Yu Xiao, Xinghuan Wang
Holliday Junction Recognition Protein (HJURP) is a centromeric histone chaperone involving in de novo histone H3 variant CenH3 (CENP-A) recruitment. Our transcriptome and in vivo study revealed that HJURP is significantly upregulated in bladder cancer (BCa) tissues at both mRNA and protein levels. Knockdown of HJURP inhibited proliferation and viability of BCa cell lines revealed by CCK-8, colony formation and Ki-67-staining assays, and induced apoptosis and reactive oxygen species (ROS) production, as well as triggered cell cycle arrest at G0/G1 phase possibly via loss of CENP-A...
2017: Journal of Cancer
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