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histone chaperone

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https://www.readbyqxmd.com/read/28522692/mitotic-chromosome-assembly-despite-nucleosome-depletion-in-xenopus-egg-extracts
#1
Keishi Shintomi, Fukashi Inoue, Hiroshi Watanabe, Keita Ohsumi, Miho Ohsugi, Tatsuya Hirano
The nucleosome is the fundamental structural units of eukaryotic chromatin. During mitosis, duplicated nucleosome fibers are organized into a pair of rod-shaped structures (chromatids) within a mitotic chromosome. However, it remains unclear whether nucleosome assembly is indeed an essential prerequisite for mitotic chromosome assembly. Here, we combined mouse sperm nuclei and Xenopus cell-free egg extracts depleted of the histone chaperone Asf1 and found that chromatid-like structures could be assembled even in the near-absence of nucleosomes...
May 18, 2017: Science
https://www.readbyqxmd.com/read/28520954/h2b-ubiquitylation-and-the-histone-chaperone-asf1-cooperatively-mediate-the-formation-and-maintenance-of-heterochromatin-silencing
#2
Meng-Ying Wu, Chia-Yeh Lin, Hsin-Yi Tseng, Fei-Man Hsu, Pao-Yang Chen, Cheng-Fu Kao
Heterochromatin is a heritable form of gene repression, with critical roles in development and cell identity. Understanding how chromatin factors results in such repression is a fundamental question. Chromatin is assembled and disassembled during transcription, replication and repair by anti-silencing function 1 (Asf1), a highly conserved histone chaperone. Transcription and DNA replication are also affected by histone modifications that modify nucleosome dynamics, such as H2B ubiquitylation (H2Bub). We report here that H2Bub and Asf1 cooperatively promote transcriptional silencing at yeast telomeres and mating loci...
May 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28515277/histone-chaperone-hira-regulates-neural-progenitor-cell-proliferation-and-neurogenesis-via-%C3%AE-catenin
#3
Yanxin Li, Jianwei Jiao
Histone cell cycle regulator (HIRA) is a histone chaperone and has been identified as an epigenetic regulator. Subsequent studies have provided evidence that HIRA plays key roles in embryonic development, but its function during early neurogenesis remains unknown. Here, we demonstrate that HIRA is enriched in neural progenitor cells, and HIRA knockdown reduces neural progenitor cell proliferation, increases terminal mitosis and cell cycle exit, and ultimately results in premature neuronal differentiation. Additionally, we demonstrate that HIRA enhances β-catenin expression by recruiting H3K4 trimethyltransferase Setd1A, which increases H3K4me3 levels and heightens the promoter activity of β-catenin...
May 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28497778/pten-regulates-glioblastoma-oncogenesis-through-chromatin-associated-complexes-of-daxx-and-histone-h3-3
#4
Jorge A Benitez, Jianhui Ma, Matteo D'Antonio, Antonia Boyer, Maria Fernanda Camargo, Ciro Zanca, Stephen Kelly, Alireza Khodadadi-Jamayran, Nathan M Jameson, Michael Andersen, Hrvoje Miletic, Shahram Saberi, Kelly A Frazer, Webster K Cavenee, Frank B Furnari
Glioblastoma (GBM) is the most lethal type of human brain cancer, where deletions and mutations in the tumour suppressor gene PTEN (phosphatase and tensin homolog) are frequent events and are associated with therapeutic resistance. Herein, we report a novel chromatin-associated function of PTEN in complex with the histone chaperone DAXX and the histone variant H3.3. We show that PTEN interacts with DAXX and, in turn PTEN directly regulates oncogene expression by modulating DAXX-H3.3 association on the chromatin, independently of PTEN enzymatic activity...
May 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28496363/prognostic-value-of-histone-chaperone-fact-subunits-expression-in-breast-cancer
#5
Kristopher Attwood, Daria Fleyshman, Laura Prendergast, Geraldine Paszkiewicz, Angela R Omilian, Wiam Bshara, Katerina Gurova
Understanding the underlying reasons for tumor aggressiveness, such as why some tumors grow slowly and locally, while others rapidly progress to a lethal metastatic disease, is still limited. This is especially critical in breast cancer (BrCa) due to its high prevalence and also due to the possibility that it can be detected early. Several oncogenes and tumor suppressors have been identified and are used in the prognosis and treatment of BrCa. However, even with these markers, the outcome within BrCa subtypes is highly variable...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28490005/opposing-effects-of-valproic-acid-treatment-mediated-by-histone-deacetylase-inhibitor-activity-in-four-transgenic-x-laevis-models-of-retinitis-pigmentosa
#6
Ruanne Y J Vent-Schmidt, Runxia H Wen, Zusheng Zong, Colette N Chiu, Beatrice M Tam, Christopher G May, Orson L Moritz
Retinitis pigmentosa (RP) is an inherited retinal degeneration (RD) that leads to blindness for which no treatment is available. RP is frequently caused by mutations in Rhodopsin; in some animal models, RD is exacerbated by light. Valproic acid (VPA) is a proposed treatment for RP and other neurodegenerative disorders, with a phase II trial for RP under way. However, the therapeutic mechanism is unclear, with minimal research supporting its use in RP. We investigated the effects of VPA on Xenopus laevis models of RP expressing human P23H, T17M, T4K, and Q344ter rhodopsins, which are associated with RP in humans...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28481984/the-dna-damage-response-ddr-is-induced-by-the-c9orf72-repeat-expansion-in-amyotrophic-lateral-sclerosis
#7
Manal A Farg, Anna Konopka, Kai Ying Soo, Daisuke Ito, Julie D Atkin
Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease affecting motor neurons. Hexanucleotide (GGGGCC) repeat expansions in a non-coding region of C9orf72 are the major cause of familial ALS and frontotemporal dementia (FTD) worldwide. The C9orf72 repeat expansion undergoes repeat-associated non-ATG (RAN) translation to produce five dipeptide repeat proteins (DRPs), including poly(GR) and poly(PR). Whilst it remains unclear how mutations in C9orf72 lead to neurodegeneration in ALS/FTD, dysfunction to the nucleolus and R loop formation are implicated as pathogenic mechanisms...
May 8, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28474205/chaperone-co-inducer-bgp-15-inhibits-histone-deacetylases-and-enhances-the-heat-shock-response-through-increased-chromatin-accessibility
#8
Marek A Budzyński, Tim Crul, Samu V Himanen, Noemi Toth, Ferenc Otvos, Lea Sistonen, Laszlo Vigh
Defects in cellular protein homeostasis are associated with many severe and prevalent pathological conditions such as neurodegenerative diseases, muscle dystrophies, and metabolic disorders. One way to counteract these defects is to improve the protein homeostasis capacity through induction of the heat shock response. Despite numerous attempts to develop strategies for chemical activation of the heat shock response by heat shock transcription factor 1 (HSF1), the underlying mechanisms of drug candidates' mode of action are poorly understood...
May 4, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28468903/residues-in-the-nucleosome-acidic-patch-regulate-histone-occupancy-and-are-important-for-fact-binding-in-saccharomyces-cerevisiae
#9
Amelia J Hodges, Lisa M Gloss, John J Wyrick
The essential histone chaperone FACT plays a critical role in DNA replication, repair, and transcription, primarily by binding to histone H2A-H2B dimers and regulating their assembly into nucleosomes. While FACT histone chaperone activity has been extensively studied, the exact nature of the H2A and H2B residues important for FACT binding remains controversial. In this study, we characterized the functions of residues in the histone H2A and H2B acidic patch, which is important for binding many chromatin-associated factors...
May 3, 2017: Genetics
https://www.readbyqxmd.com/read/28465257/5-fluorouracil-targets-histone-acetyltransferases-p300-cbp-in-the-treatment-of-colorectal-cancer
#10
Changzheng Du, Dandan Huang, Yifan Peng, Yunfeng Yao, Ying Zhao, Yang Yang, Haiying Wang, Linlin Cao, Wei-Guo Zhu, Jin Gu
Although 5-fluorouracil (5-FU) is known to interfere with the synthesis of ribonucleic acid and deoxyribonucleic acid, the mechanism underlying its therapeutic efficacy in colorectal cancer (CRC) has not been fully elucidated. We aimed to investigate the influence of 5-FU on histone acetylation, a well-established anti-cancer target, to reveal novel pharmacological effects of 5-FU and their significance for CRC therapy. Results demonstrated that 5-FU induces global histone de-acetylation in multiple CRC cell lines...
April 29, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28443118/the-absence-of-the-arabidopsis-chaperone-complex-caf-1-produces-mitotic-chromosome-abnormalities-and-changes-in-the-expression-profiles-of-genes-involved-in-dna-repair
#11
Javier Varas, Juan L Santos, Mónica Pradillo
Chromatin Assembly Factor 1 (CAF-1) is an evolutionary conserved heterotrimeric chaperone complex that facilitates the incorporation of histones H3 and H4 onto newly synthesized DNA. We demonstrate here that the mutant deficient for the large subunit of the complex, fas1-4, and in minor extent, the mutant deficient for the middle subunit, fas2-1, display chromosome abnormalities throughout Arabidopsis mitosis. Among them, we observed multicentromeric chromosomes at metaphase, and chromatid bridges and acentric fragments at anaphase-telophase...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28423528/level-of-fact-defines-the-transcriptional-landscape-and-aggressive-phenotype-of-breast-cancer-cells
#12
Daria Fleyshman, Laura Prendergast, Alfiya Safina, Geraldine Paszkiewicz, Mairead Commane, Kelsey Morgan, Kristopher Attwood, Katerina Gurova
Although breast cancer (BrCa) may be detected at an early stage, there is a shortage of markers that predict tumor aggressiveness and a lack of targeted therapies. Histone chaperone FACT, expressed in a limited number of normal cells, is overexpressed in different types of cancer, including BrCa. Recently, we found that FACT expression in BrCa correlates with markers of aggressive BrCa, which prompted us to explore the consequences of FACT inhibition in BrCa cells with varying levels of FACT.FACT inhibition using a small molecule or shRNA caused reduced growth and viability of all BrCa cells tested...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419835/the-architecture-and-function-of-the-chromatin-replication-machinery
#13
REVIEW
Thomas Cr Miller, Alessandro Costa
Genomic DNA in eukaryotic cells is packaged into nucleosome arrays. During replication, nucleosomes need to be dismantled ahead of the advancing replication fork and reassembled on duplicated DNA. The architecture and function of the core replisome machinery is now beginning to be elucidated, with recent insights shaping our view on DNA replication processes. Simultaneously, breakthroughs in our mechanistic understanding of epigenetic inheritance allow us to build new models of how histone chaperones integrate with the replisome to reshuffle nucleosomes...
April 15, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28418026/the-cac2-subunit-is-essential-for-productive-histone-binding-and-nucleosome-assembly-in-caf-1
#14
Francesca Mattiroli, Yajie Gu, Jeremy L Balsbaugh, Natalie G Ahn, Karolin Luger
Nucleosome assembly following DNA replication controls epigenome maintenance and genome integrity. Chromatin assembly factor 1 (CAF-1) is the histone chaperone responsible for histone (H3-H4)2 deposition following DNA synthesis. Structural and functional details for this chaperone complex and its interaction with histones are slowly emerging. Using hydrogen-deuterium exchange coupled to mass spectrometry, combined with in vitro and in vivo mutagenesis studies, we identified the regions involved in the direct interaction between the yeast CAF-1 subunits, and mapped the CAF-1 domains responsible for H3-H4 binding...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28416484/ssrp1-cooperates-with-parp-and-xrcc1-to-facilitate-single-strand-dna-break-repair-by-chromatin-priming
#15
Ying Gao, Changling Li, Leizhen Wei, Yaqun Teng, Satoshi Nakajima, Xiukai Chen, Jianquan Xu, Brittany Leger, Hongqiang Ma, Stephen Spagnol, Yong Wan, Kris Dahl, Yang Liu, Arthur Levine, Li Lan
DNA single strand breaks (SSB) are the most common form of DNA damage, requiring repair processes that to initiate must overcome chromatin barriers. The FACT complex comprised of the SSRP1 and SPT16 proteins are important for maintaining chromatin integrity, with SSRP1 acting as an histone H2A/H2B chaperone in chromatin disassembly during DNA transcription, replication and repair. In this study, we show that SSRP1 but not SPT16 is critical for cell survival after ionizing radiation or methyl methanesulfonate-induced single-strand DNA damage...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28401892/notch-and-hippo-signaling-converge-on-strawberry-notch-1-sbno1-to-synergistically-activate-cdx2-during-specification-of-the-trophectoderm
#16
Yusuke Watanabe, Kota Y Miyasaka, Atsushi Kubo, Yasuyuki S Kida, Osamu Nakagawa, Yoshikazu Hirate, Hiroshi Sasaki, Toshihiko Ogura
The first binary cell fate decision occurs at the morula stage and gives rise to two distinct types of cells that constitute the trophectoderm (TE) and inner cell mass (ICM). The cell fate determinant, Cdx2, is induced in TE cells and plays an essential role in their differentiation and maintenance. Notch and Hippo signaling cascades are assumed to converge onto regulatory elements of Cdx2, however, the underlying molecular mechanisms are largely unknown. Here, we show involvement of Strawberry Notch1 (Sbno1), a novel chromatin factor of the helicase superfamily 2, during preimplantation development...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28398261/novel-proteasome-inhibitors-and-histone-deacetylase-inhibitors-progress-in-myeloma-therapeutics
#17
REVIEW
Saurabh Chhabra
The unfolded protein response is responsible for the detection of misfolded proteins and the coordination of their disposal and is necessary to maintain the cellular homoeostasis. Multiple myeloma cells secrete large amounts of immunoglobulins, proteins that need to be correctly folded by the chaperone system. If this process fails, the misfolded proteins have to be eliminated by the two main garbage-disposal systems of the cell: proteasome and aggresome. The blockade of either of these systems will result in accumulation of immunoglobulins and other toxic proteins in the cytoplasm and cell death...
April 11, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28386352/clusterin-signals-via-apoer2-vldlr-and-induces-meiosis-of-male-germ-cells
#18
Muhammad Assad Riaz, Angelika Stammler, Mareike Borgers, Lutz Konrad
Clusterin (CLU) is a ubiquitously expressed heterodimeric glycoprotein that is involved in a variety of functions like cell-cell interactions, apoptosis, epithelial-mesenchymal transition, carcinogenesis, and chaperone function. In the testis, CLU is strongly expressed especially in Sertoli cells but very little is known about its testicular function, regulation of secretion and most enigmatic, its receptor(s). In this study, we approached these questions with a special emphasis on the link between CLU and meiosis...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28381790/the-wd40-domain-of-hira-is-essential-for-ri-nucleosome-assembly-in-xenopus-egg-extracts
#19
Ruibin Zhu, Mari Iwabuchi, Keita Ohsumi
Histone chaperones are a group of histone-binding proteins that facilitate the assembly of nucleosomes, the fundamental structural units of chromatin in eukaryotes. In nucleosome assembly, deposition of a histone H3-H4 tetramer onto DNA is the first and critical step, which is mediated by the histone chaperones HIRA and CAF-1. HIRA and CAF-1 are reportedly involved in DNA replication independent (RI) and replication coupled nucleosome assembly, respectively. However, the mechanisms by which they mediate histone deposition remain unclear...
2017: Cell Structure and Function
https://www.readbyqxmd.com/read/28369616/nap1l1-accelerates-activation-and-decreases-pausing-to-enhance-nucleosome-remodeling-by-csb
#20
Ju Yeon Lee, Robert J Lake, Jaewon Kirk, Vilhelm A Bohr, Hua-Ying Fan, Sungchul Hohng
Cockayne syndrome protein B (CSB) belongs to the SWI2/SNF2 ATP-dependent chromatin remodeler family, and CSB is the only ATP-dependent chromatin remodeler essential for transcription-coupled nucleotide excision DNA repair. CSB alone remodels nucleosomes ∼10-fold slower than the ACF remodeling complex. Strikingly, NAP1-like histone chaperones interact with CSB and greatly enhance CSB-mediated chromatin remodeling. While chromatin remodeling by CSB and NAP1-like proteins is crucial for efficient transcription-coupled DNA repair, the mechanism by which NAP1-like proteins enhance chromatin remodeling by CSB remains unknown...
May 5, 2017: Nucleic Acids Research
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