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https://www.readbyqxmd.com/read/28934480/hydroxyl-radical-footprinting-combined-with-molecular-modeling-identifies-unique-features-of-dna-conformation-and-nucleosome-positioning
#1
Alexey K Shaytan, Hua Xiao, Grigoriy A Armeev, Carl Wu, David Landsman, Anna R Panchenko
Nucleosomes are the most abundant protein-DNA complexes in eukaryotes that provide compaction of genomic DNA and are implicated in regulation of transcription, DNA replication and repair. The details of DNA positioning on the nucleosome and the DNA conformation can provide key regulatory signals. Hydroxyl-radical footprinting (HRF) of protein-DNA complexes is a chemical technique that probes nucleosome organization in solution with a high precision unattainable by other methods. In this work we propose an integrative modeling method for constructing high-resolution atomistic models of nucleosomes based on HRF experiments...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934465/regulation-of-chromatin-folding-by-conformational-variations-of-nucleosome-linker-dna
#2
Jenna M Buckwalter, Davood Norouzi, Anna Harutyunyan, Victor B Zhurkin, Sergei A Grigoryev
Linker DNA conformational variability has been proposed to direct nucleosome array folding into more or less compact chromatin fibers but direct experimental evidence for such models are lacking. Here, we tested this hypothesis by designing nucleosome arrays with A-tracts at specific locations in the nucleosome linkers to induce inward (AT-IN) and outward (AT-OUT) bending of the linker DNA. Using electron microscopy and analytical centrifugation techniques, we observed spontaneous folding of AT-IN nucleosome arrays into highly compact structures, comparable to those induced by linker histone H1...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28933282/molecular-mechanisms-of-epigenetic-regulators-as-activatable-targets-in-cancer-theranostics
#3
Yinglu Li, Zhiming Li, Wei-Guo Zhu
Epigenetics is defined as somatically inheritable changes that are not accompanied by alterations in DNA sequence. Epigenetics encompasses DNA methylation, covalent histone modifications, non-coding RNA as well as nucleosome remodeling. Notably, abnormal epigenetic changes play a critical role in cancer development including malignant transformation, metastasis, prognosis, drug resistance and tumor recurrence, which can provide effective targets for cancer prognosis, diagnosis and therapy. Understanding these changes provide effective means for cancer diagnosis and druggable targets for better clinical applications...
September 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28931432/hypomethylated-domain-enriched-dna-motifs-prepattern-the-accessible-nucleosome-organization-in-teleosts
#4
Ryohei Nakamura, Ayako Uno, Masahiko Kumagai, Shinichi Morishita, Hiroyuki Takeda
BACKGROUND: Gene promoters in vertebrate genomes show distinct chromatin features such as stably positioned nucleosome array and DNA hypomethylation. The nucleosomes are known to have certain sequence preferences, and the prediction of nucleosome positioning from DNA sequence has been successful in some organisms such as yeast. However, at gene promoters where nucleosomes are much more stably positioned than in other regions, the sequence-based model has failed to work well, and sequence-independent mechanisms have been proposed...
September 20, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28930672/histone-h3-methylated-at-arginine-17-is-essential-for-reprogramming-the-paternal-genome-in-zygotes
#5
Yuki Hatanaka, Takeshi Tsusaka, Natsumi Shimizu, Kohtaro Morita, Takehiro Suzuki, Shinichi Machida, Manabu Satoh, Arata Honda, Michiko Hirose, Satoshi Kamimura, Narumi Ogonuki, Toshinobu Nakamura, Kimiko Inoue, Yoshihiko Hosoi, Naoshi Dohmae, Toru Nakano, Hitoshi Kurumizaka, Kazuya Matsumoto, Yoichi Shinkai, Atsuo Ogura
At fertilization, the paternal genome undergoes extensive reprogramming through protamine-histone exchange and active DNA demethylation, but only a few maternal factors have been defined in these processes. We identified maternal Mettl23 as a protein arginine methyltransferase (PRMT), which most likely catalyzes the asymmetric dimethylation of histone H3R17 (H3R17me2a), as indicated by in vitro assays and treatment with TBBD, an H3R17 PRMT inhibitor. Maternal histone H3.3, which is essential for paternal nucleosomal assembly, is unable to be incorporated into the male pronucleus when it lacks R17me2a...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28927461/additional-sex-combs-interacts-with-enhancer-of-zeste-and-trithorax-and-modulates-levels-of-trimethylation-on-histone-h3k4-and-h3k27-during-transcription-of-hsp70
#6
Taosui Li, Jacob W Hodgson, Svetlana Petruk, Alexander Mazo, Hugh W Brock
BACKGROUND: Maintenance of cell fate determination requires the Polycomb group for repression; the trithorax group for gene activation; and the enhancer of trithorax and Polycomb (ETP) group for both repression and activation. Additional sex combs (Asx) is a genetically identified ETP for the Hox loci, but the molecular basis of its dual function is unclear. RESULTS: We show that in vitro, Asx binds directly to the SET domains of the histone methyltransferases (HMT) enhancer of zeste [E(z)] (H3K27me3) and Trx (H3K4me3) through a bipartite interaction site separated by 846 amino acid residues...
September 19, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28926429/targeting-histone-acetylation-readers-and-writers-in-leukemia-and-cancer
#7
Christopher B Benton, Warren Fiskus, Kapil N Bhalla
Chromatin packaging of DNA provides a framework for transcriptional regulation. Modifications to DNA and histone proteins in nucleosomes lead to conformational changes, alterations in the recruitment of transcriptional complexes, and ultimately modulation of gene expression. We provide a focused review of control mechanisms that help modulate the activation and deactivation of gene transcription specifically through histone acetylation writers and readers in cancer. The chemistry of these modifications is subject to clinically actionable targeting, including state-of-the-art strategies to inhibit basic oncogenic mechanisms related to histone acetylation...
September 2017: Cancer Journal
https://www.readbyqxmd.com/read/28925811/it-s-fun-to-transcribe-with-fun30-a-model-for-nucleosome-dynamics-during-rna-polymerase-ii-mediated-elongation
#8
Junwoo Lee, Eun Shik Choi, Daeyoup Lee
The ability of elongating RNA polymerase II (RNAPII) to regulate the nucleosome barrier is poorly understood because we do not know enough about the involved factors and we lack a conceptual framework to model this process. Our group recently identified the conserved Fun30/SMARCAD1 family chromatin-remodeling factor, Fun30(Fft3), as being critical for relieving the nucleosome barrier during RNAPII-mediated elongation, and proposed a model illustrating how Fun30(Fft3) may contribute to nucleosome disassembly during RNAPII-mediated elongation...
September 19, 2017: Transcription
https://www.readbyqxmd.com/read/28924382/linker-histone-in-diseases
#9
REVIEW
Xin Ye, ChuanLin Feng, Tian Gao, Guanqun Mu, Weiguo Zhu, Yang Yang
The linker histone is a protein that binds with the nucleosome, which is generally considered to achieve chromatin condensation in the nucleus. Accumulating evidences suggest that the linker histone is essential in the pathogenesis of several diseases. In this review, we briefly introduce the current knowledge of the linker histone, including its structure, characteristics and functions. Also, we move forward to present the advances of the linker histone's association with certain diseases, such as cancer, Alzheimer's disease, infection, male infertility and aberrant immunity situations, focusing on the alteration of the linker histone under certain pathological conditions and its role in developing each disease...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28920961/germline-mutations-affecting-the-histone-h4-core-cause-a-developmental-syndrome-by-altering-dna-damage-response-and-cell-cycle-control
#10
Federico Tessadori, Jacques C Giltay, Jane A Hurst, Maarten P Massink, Karen Duran, Harmjan R Vos, Robert M van Es, Richard H Scott, Koen L I van Gassen, Jeroen Bakkers, Gijs van Haaften
Covalent modifications of histones have an established role as chromatin effectors, as they control processes such as DNA replication and transcription, and repair or regulate nucleosomal structure. Loss of modifications on histone N tails, whether due to mutations in genes belonging to histone-modifying complexes or mutations directly affecting the histone tails, causes developmental disorders or has a role in tumorigenesis. More recently, modifications affecting the globular histone core have been uncovered as being crucial for DNA repair, pluripotency and oncogenesis...
September 18, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28917635/evolutionary-analysis-of-nucleosome-positioning-sequences-based-on-new-symmetric-relative-entropy
#11
Hu Meng, Hong Li, Yan Zheng, Zhenhua Yang, Yun Jia, Suling Bo
New Symmetric Relative Entropy (NSRE) was applied innovatively to analyze the nucleosome sequences in S. cerevisiae, S. pombe and Drosophila. NSRE distributions could well reflect the characteristic differences of nucleosome sequences among three organisms, and the differences indicate a concerted evolution in the sequence usage of nucleosome. Further analysis about the nucleosomes around TSS shows that the constitutive property of +1/-1 nucleosomes in S. cerevisiae is different from that in S. pombe and Drosophila, which indicates that S...
September 13, 2017: Genomics
https://www.readbyqxmd.com/read/28916288/anti-apoptotic-and-moderate-anti-inflammatory-effects-of-berberine-in-sulfur-mustard-exposed-keratinocytes
#12
Simon Lang, Tanja Popp, Christian Silvester Kriegs, Annette Schmidt, Frank Balszuweit, Georg Menacher, Kai Kehe, Horst Thiermann, Thomas Gudermann, Dirk Steinritz
Skin affections after sulfur mustard (SM) exposure include erythema, blister formation and severe inflammation. An antidote or specific therapy does not exist. Anti-inflammatory compounds as well as substances counteracting SM-induced cell death are under investigation. In this study, we investigated the benzylisoquinoline alkaloide berberine (BER), a metabolite in plants like berberis vulgaris, which is used as herbal pharmaceutical in Asian countries, against SM toxicity using a well-established in vitro approach...
September 12, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28914995/silencing-hmgn5-suppresses-cell-growth-and-promotes-chemosensitivity-in-esophageal-squamous-cell-carcinoma
#13
Xiaoping Liu, Weiping Ma, Yanli Yan, Suge Wu
Previous study has demonstrated that high mobility group nucleosome-binding domain 5 (HMGN5) is involved in tumorigenesis and the development of multidrug resistance in several human cancers. However, the role of HMGN5 in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we showed that HMGN5 was significantly upregulated in ESCC cells. Knockdown of HMGN5 significantly inhibited cell growth and induced cell apoptosis of ESCC cells. Moreover, knockdown of HMGN5 increased the sensitivity of ESCC cells towards cisplatin...
September 15, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28912563/a-cell-cycle-independent-mode-of-the-rad9-dpb11-interaction-is-induced-by-dna-damage
#14
Giulia di Cicco, Susanne C S Bantele, Karl-Uwe Reusswig, Boris Pfander
Budding yeast Rad9, like its orthologs, controls two aspects of the cellular response to DNA double strand breaks (DSBs) - signalling of the DNA damage checkpoint and DNA end resection. Rad9 binds to damaged chromatin via modified nucleosomes independently of the cell cycle phase. Additionally, Rad9 engages in a cell cycle-regulated interaction with Dpb11 and the 9-1-1 clamp, generating a second pathway that recruits Rad9 to DNA damage sites. Binding to Dpb11 depends on specific S/TP phosphorylation sites of Rad9, which are modified by cyclin-dependent kinase (CDK)...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912372/genome-wide-maps-of-alkylation-damage-repair-and-mutagenesis-in-yeast-reveal-mechanisms-of-mutational-heterogeneity
#15
Peng Mao, Alexander J Brown, Ewa P Malc, Piotr A Mieczkowski, Michael J Smerdon, Steven A Roberts, John J Wyrick
DNA base damage is an important contributor to genome instability, but how the formation and repair of these lesions is affected by the genomic landscape and contributes to mutagenesis is unknown. Here, we describe genome-wide maps of DNA base damage, repair, and mutagenesis at single nucleotide resolution in yeast treated with the alkylating agent methyl methanesulfonate (MMS). Analysis of these maps revealed that base excision repair (BER) of alkylation damage is significantly modulated by chromatin, with faster repair in nucleosome-depleted regions, and slower repair and higher mutation density within strongly positioned nucleosomes...
September 14, 2017: Genome Research
https://www.readbyqxmd.com/read/28911106/unencumbered-pol-%C3%AE-lyase-activity-in-nucleosome-core-particles
#16
Yesenia Rodriguez, Michael J Howard, Matthew J Cuneo, Rajendra Prasad, Samuel H Wilson
Packaging of DNA into the nucleosome core particle (NCP) is considered to exert constraints to all DNA-templated processes, including base excision repair where Pol β catalyzes two key enzymatic steps: 5'-dRP lyase gap trimming and template-directed DNA synthesis. Despite its biological significance, knowledge of Pol β activities on NCPs is still limited. Here, we show that removal of the 5'-dRP block by Pol β is unaffected by NCP constraints at all sites tested and is even enhanced near the DNA ends. In contrast, strong inhibition of DNA synthesis is observed...
September 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28910577/subnuclear-distribution-of-proteins-links-with-genome-architecture
#17
Fouziya R Shah, Younus A Bhat, Ajazul H Wani
Metazoan genomes have a hierarchal 3-dimensional (3D) organization scaling from nucleosomes, loops, topologically associating domains (TADs), compartments, to chromosome territories. The 3D organization of genome has been linked with development, differentiation and disease. However, the principles governing the 3D chromatin architecture are just beginning to get unraveled. The nucleus has very high concentration of proteins and these proteins are either diffusely distributed throughout the nucleus, or aggregated in the form of foci/bodies/clusters/speckles or in combination of both...
September 14, 2017: Nucleus
https://www.readbyqxmd.com/read/28904333/the-ino80-complex-mediates-epigenetic-centromere-propagation-via-active-removal-of-histone-h3
#18
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/28902852/genome-wide-chromatin-mapping-with-size-resolution-reveals-a-dynamic-sub-nucleosomal-landscape-in-arabidopsis
#19
Daniel Antony Pass, Emily Sornay, Angela Marchbank, Margaret R Crawford, Konrad Paszkiewicz, Nicholas A Kent, James A H Murray
All eukaryotic genomes are packaged as chromatin, with DNA interlaced with both regularly patterned nucleosomes and sub-nucleosomal-sized protein structures such as mobile and labile transcription factors (TF) and initiation complexes, together forming a dynamic chromatin landscape. Whilst details of nucleosome position in Arabidopsis have been previously analysed, there is less understanding of their relationship to more dynamic sub-nucleosomal particles (subNSPs) defined as protected regions shorter than the ~150bp typical of nucleosomes...
September 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28899943/the-chromatin-remodeling-isw1a-complex-is-regulated-by-sumoylation
#20
Qingtang Shen, Nissrine Beyrouthy, Laura Matabishi-Bibi, Catherine Dargemont
The ISWI class of proteins consists in a family of chromatin remodeling ATPases that is ubiquitous in eukaryotes and predominantly functions to slide nucleosomes laterally. The yeast Saccharomyces cerevisiae Isw1 partners with several non-essential alternative subunits-Ioc2, Ioc3, or Ioc4-to form two distinct complexes Isw1a and Isw1b. Besides its ATPase domain, Isw1 presents a C-terminal region formed by HAND, SANT and SLIDE domains responsible for interaction with the Ioc proteins and optimal association of Isw1 to chromatin...
September 12, 2017: Biochemical Journal
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