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https://www.readbyqxmd.com/read/29792694/biomimetic-artificial-epigenetic-code-for-targeted-acetylation-of-histones
#1
Junichi Taniguchi, Yihong Feng, Ganesh N Pandian, Fumitaka Hashiya, Takuya Hidaka, Kaori Hashiya, Soyoung Park, Toshikazu Bando, Shinji Ito, Hiroshi Sugiyama
While the central role of locus-specific acetylation of histone proteins in eukaryotic gene expression is well established, the availability of designer tools to regulate acetylation at particular nucleosome sites remains limited. Here, we develop a unique strategy to introduce acetylation by constructing a bifunctional molecule designated Bi-PIP. Bi-PIP has a P300/CBP-selective bromodomain inhibitor (Bi) as a P300/CBP recruiter and a pyrrole-imidazole polyamide (PIP) as a sequence-selective DNA binder. Biochemical assays verified that Bi-PIPs recruit P300 to the nucleosomes having their target DNA sequences and extensively accelerate acetylation...
May 24, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29685973/epigenetic-drug-discovery-a-success-story-for-cofactor-interference
#2
REVIEW
A Ganesan
Within the past two decades, seven epigenetic drugs have received regulatory approval and numerous other candidates are currently in clinical trials. Among the epigenetic targets are the writer and eraser enzymes that are, respectively, responsible for the reversible introduction and removal of structural modifications in the nucleosome. This review discusses the progress achieved in the design and development of inhibitors against the key writer and eraser pairs: DNA methyltransferases and Tet demethylases; lysine/arginine methyltransferases and lysine demethylases; and histone acetyltransferases and histone deacetylases...
June 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29678692/nucpospred-predicting-species-specific-genomic-nucleosome-positionin-g-via-four-different-modes-of-general-pseknc
#3
Cangzhi Jia, Qing Yang, Quan Zou
The nucleosome is the basic structure of chromatin in eukaryotic cells, with essential roles in the regulation of many biological processes, such as DNA transcription, replication and repair, and RNA splicing. Because of the importance of nucleosomes, the factors that determine their positioning within genomes should be investigated. High-resolution nucleosome-positioning maps are now available for organisms including Saccharomyces cerevisiae, Drosophila melanogaster and Caenorhabditis elegans, enabling the identification of nucleosome positioning by application of computational tools...
April 17, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29644260/biochemical-analysis-of-dimethyl-suberimidate-crosslinked-yeast-nucleosomes
#4
Yuichi Ichiakwa, Paul D Kaufman
Nucleosomes are the fundamental unit of eukaryotic chromosome packaging, comprised of 147 bp of DNA wrapped around two molecules of each of the core histone proteins H2A, H2B, H3, and H4. Nucleosomes are symmetrical, with one axis of symmetry centered on the homodimeric interaction between the C-termini of the H3 molecules. To explore the functional consequences of nucleosome symmetry, we designed an obligate pair of H3 heterodimers, termed H3X and H3Y, allowing us to compare cells with single or double H3 alterations...
March 20, 2018: Bio-protocol
https://www.readbyqxmd.com/read/29642840/iseg-an-efficient-algorithm-for-segmentation-of-genomic-and-epigenomic-data
#5
Senthil B Girimurugan, Yuhang Liu, Pei-Yau Lung, Daniel L Vera, Jonathan H Dennis, Hank W Bass, Jinfeng Zhang
BACKGROUND: Identification of functional elements of a genome often requires dividing a sequence of measurements along a genome into segments where adjacent segments have different properties, such as different mean values. Despite dozens of algorithms developed to address this problem in genomics research, methods with improved accuracy and speed are still needed to effectively tackle both existing and emerging genomic and epigenomic segmentation problems. RESULTS: We designed an efficient algorithm, called iSeg, for segmentation of genomic and epigenomic profiles...
April 11, 2018: BMC Bioinformatics
https://www.readbyqxmd.com/read/29605855/defining-regulatory-elements-in-the-human-genome-using-nucleosome-occupancy-and-methylome-sequencing-nome-seq
#6
Suhn Kyong Rhie, Shannon Schreiner, Peggy J Farnham
NOMe-seq (nucleosome occupancy and methylome sequencing) identifies nucleosome-depleted regions that correspond to promoters, enhancers, and insulators. The NOMe-seq method is based on the treatment of chromatin with the M.CviPI methyltransferase, which methylates GpC dinucleotides that are not protected by nucleosomes or other proteins that are tightly bound to the chromatin (GpCm does not occur in the human genome and therefore there is no endogenous background of GpCm ). Following bisulfite treatment of the M...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29589929/investigating-the-dynamics-of-destabilized-nucleosomes-using-methyl-trosy-nmr
#7
Julianne L Kitevski-LeBlanc, Tairan Yuwen, Pamela N Dyer, Johannes Rudolph, Karolin Luger, Lewis E Kay
The nucleosome core particle (NCP), comprised of histone proteins wrapped with ∼146 base pairs of DNA, provides both protection and controlled access to DNA so as to regulate vital cellular processes. High-resolution structures of nucleosomes and nucleosome complexes have afforded a clear understanding of the structural role of NCPs, but a detailed description of the dynamical properties that facilitate DNA-templated processes is only beginning to emerge. Using methyl-TROSY NMR approaches we evaluate the effect of point mutations designed to perturb key histone interfaces that become destabilized during nucleosome remodeling in an effort to probe NCP plasticity...
March 28, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29571055/nucleosome-inspired-nanocarrier-obtains-encapsulation-efficiency-enhancement-and-side-effects-reduction-in-chemotherapy-by-using-fullerenol-assembled-with-doxorubicin
#8
Jinglong Tang, Ruirui Zhang, Mengyu Guo, Leihou Shao, Ying Liu, Yuliang Zhao, Suojiang Zhang, Yan Wu, Chunying Chen
Chemodrugs have been widely used to treat cancer; however, the chemotherapy usually leads to serious side effects and failure. Various nanomaterials and strategies have been explored for drug delivery to improve the efficacy of chemodrugs. One key to loading chemodrugs onto a nano-delivery system is enhancement of the encapsulation efficiency, especially for polymeric nanoparticles being loaded with hydrophilic drugs. Inspired by the ability of eukaryote to package millions of genes in the nucleus wrapping and condensing DNA around histones to form chromosomes, here we developed a karyon-like hybrid nanoparticle to achieve ultra-high encapsulation of doxorubicin (Dox) with reduced side effects...
June 2018: Biomaterials
https://www.readbyqxmd.com/read/29509191/chip-seq-and-chip-exo-profiling-of-pol-ii-h2a-z-and-h3k4me3-in-human-k562-cells
#9
Zenab F Mchaourab, Andrea A Perreault, Bryan J Venters
The human K562 chronic myeloid leukemia cell line has long served as an experimental paradigm for functional genomic studies. To systematically and functionally annotate the human genome, the ENCODE consortium generated hundreds of functional genomic data sets, such as chromatin immunoprecipitation coupled to sequencing (ChIP-seq). While ChIP-seq analyses have provided tremendous insights into gene regulation, spatiotemporal insights were limited by a resolution of several hundred base pairs. ChIP-exonuclease (ChIP-exo) is a refined version of ChIP-seq that overcomes this limitation by providing higher precision mapping of protein-DNA interactions...
March 6, 2018: Scientific Data
https://www.readbyqxmd.com/read/29501025/synthetic-post-translational-modification-of-histones
#10
REVIEW
Simon Nadal, Ritu Raj, Shabaz Mohammed, Benjamin G Davis
Chromatin is the physiological template of genetic information in all eukaryotic cells, a highly organised complex of DNA and histone proteins central in regulating gene expression and genome organisation. A multitude of histone post-translational modifications (PTMs) have been discovered, providing a glance into the complex interplay of these epigenetic marks in cellular processes. In the last decade, synthetic and chemical biology techniques have emerged to study these modifications, including genetic code expansion, histone semisynthesis and post-translational chemical mutagenesis...
February 28, 2018: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29063705/refinement-of-the-subunit-interaction-network-within-the-nucleosome-remodelling-and-deacetylase-nurd-complex
#11
Mario Torrado, Jason K K Low, Ana P G Silva, Jason W Schmidberger, Maryam Sana, Mehdi Sharifi Tabar, Musa E Isilak, Courtney S Winning, Cherry Kwong, Max J Bedward, Mary J Sperlazza, David C Williams, Nicholas E Shepherd, Joel P Mackay
The nucleosome remodelling and deacetylase (NuRD) complex is essential for the development of complex animals. NuRD has roles in regulating gene expression and repairing damaged DNA. The complex comprises at least six proteins with two or more paralogues of each protein routinely identified when the complex is purified from cell extracts. To understand the structure and function of NuRD, a map of direct subunit interactions is needed. Dozens of published studies have attempted to define direct inter-subunit connectivities...
December 2017: FEBS Journal
https://www.readbyqxmd.com/read/29027167/characterization-of-the-nucleosome-landscape-by-micrococcal-nuclease-sequencing-mnase-seq
#12
Wieteke Anna Maria Hoeijmakers, Richárd Bártfai
MNase-seq allows the genome-wide examination of the nucleosome landscape by determination of nucleosome positioning and occupancy. Typically, native or formaldehyde fixed chromatin is subjected to digestion by micrococcal nuclease (MNase), which degrades linker DNA and yields mainly mono-nucleosomes. The resulting material can be processed directly or can be subjected to an optional chromatin immunoprecipitation step (MNase-ChIP-seq). De-crosslinked and purified DNA is then subjected to next-generation sequencing...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29021563/non-canonical-reader-modules-of-baz1a-promote-recovery-from-dna-damage
#13
Mariano Oppikofer, Meredith Sagolla, Benjamin Haley, Hui-Min Zhang, Sarah K Kummerfeld, Jawahar Sudhamsu, E Megan Flynn, Tianyi Bai, Jennifer Zhang, Claudio Ciferri, Andrea G Cochran
Members of the ISWI family of chromatin remodelers mobilize nucleosomes to control DNA accessibility and, in some cases, are required for recovery from DNA damage. However, it remains poorly understood how the non-catalytic ISWI subunits BAZ1A and BAZ1B might contact chromatin to direct the ATPase SMARCA5. Here, we find that the plant homeodomain of BAZ1A, but not that of BAZ1B, has the unusual function of binding DNA. Furthermore, the BAZ1A bromodomain has a non-canonical gatekeeper residue and binds relatively weakly to acetylated histone peptides...
October 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28934465/regulation-of-chromatin-folding-by-conformational-variations-of-nucleosome-linker-dna
#14
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/28895528/a-synthetic-biology-approach-to-probing-nucleosome-symmetry
#15
Yuichi Ichikawa, Caitlin F Connelly, Alon Appleboim, Thomas Cr Miller, Hadas Jacobi, Nebiyu A Abshiru, Hsin-Jung Chou, Yuanyuan Chen, Upasna Sharma, Yupeng Zheng, Paul M Thomas, Hsuiyi V Chen, Vineeta Bajaj, Christoph W Müller, Neil L Kelleher, Nir Friedman, Daniel Na Bolon, Oliver J Rando, Paul D Kaufman
The repeating subunit of chromatin, the nucleosome, includes two copies of each of the four core histones, and several recent studies have reported that asymmetrically-modified nucleosomes occur at regulatory elements in vivo. To probe the mechanisms by which histone modifications are read out, we designed an obligate pair of H3 heterodimers, termed H3X and H3Y, which we extensively validated genetically and biochemically. Comparing the effects of asymmetric histone tail point mutants with those of symmetric double mutants revealed that a single methylated H3K36 per nucleosome was sufficient to silence cryptic transcription in vivo...
September 12, 2017: ELife
https://www.readbyqxmd.com/read/28855339/role-of-remodeling-and-spacing-factor-1-in-histone-h2a-ubiquitination-mediated-gene-silencing
#16
Zhuo Zhang, Amanda E Jones, Wei Wu, Jinman Kim, Yue Kang, Xiaobao Bi, Yue Gu, Ivan K Popov, Matthew B Renfrow, Marina N Vassylyeva, Dmitry G Vassylyev, Keith E Giles, Dongquan Chen, Ashwath Kumar, Yuhong Fan, Yufeng Tong, Chuan-Fa Liu, Woojin An, Chenbei Chang, Jianjun Luo, Louise T Chow, Hengbin Wang
Posttranslational histone modifications play important roles in regulating chromatin-based nuclear processes. Histone H2AK119 ubiquitination (H2Aub) is a prevalent modification and has been primarily linked to gene silencing. However, the underlying mechanism remains largely obscure. Here we report the identification of RSF1 (remodeling and spacing factor 1), a subunit of the RSF complex, as a H2Aub binding protein, which mediates the gene-silencing function of this histone modification. RSF1 associates specifically with H2Aub, but not H2Bub nucleosomes, through a previously uncharacterized and obligatory region designated as ubiquitinated H2A binding domain...
September 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28771342/yeast-terminator-function-can-be-modulated-and-designed-on-the-basis-of-predictions-of-nucleosome-occupancy
#17
Nicholas J Morse, Madan R Gopal, James M Wagner, Hal S Alper
The design of improved synthetic parts is a major goal of synthetic biology. Mechanistically, nucleosome occupancy in the 3' terminator region of a gene has been found to correlate with transcriptional expression. Here, we seek to establish a predictive relationship between terminator function and predicted nucleosome positioning to design synthetic terminators in the yeast Saccharomyces cerevisiae. In doing so, terminators improved net protein output from these expression cassettes nearly 4-fold over their original sequence with observed increases in termination efficiency to 96%...
November 17, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28695515/parp-1-interaction-with-and-activation-by-histones-and-nucleosomes
#18
Colin Thomas, Elena Kotova, Alexei V Tulin
Poly(ADP-ribose) Polymerase 1 (PARP-1) is an abundant chromatin associated protein, typical for most eukaryotic nuclei. The localization of PARP-1 in chromatin and its enzymatic activation involves multiple interactions of PARP-1 with nucleosomal histones, other proteins, and DNA. We report a set of methods designed to reconstitute PARP-1 regulation in vitro. These methods involve the expression of PARP-1 and PARP-1-regulating proteins using bacterial and eukaryotic systems, purification of these proteins using chromatography, testing of individual interactions in vitro, assembly of active complexes, and reconstitution of PARP-1 regulating reactions in vitro...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28635365/nucleosomal-organization-and-dna-base-composition-patterns
#19
REVIEW
Alicia García, Sara González, Francisco Antequera
Nucleosomes are the basic units of chromatin. They compact the genome inside the nucleus and regulate the access of proteins to DNA. In the yeast genome, most nucleosomes occupy well-defined positions, which are maintained under many different physiological situations and genetic backgrounds. Although several short sequence elements have been described that favor or reduce the affinity between histones and DNA, the extent to which the DNA sequence affects nucleosome positioning in the genomic context remains unclear...
September 3, 2017: Nucleus
https://www.readbyqxmd.com/read/28618598/designing-nucleosomal-force-sensors
#20
M Tompitak, L de Bruin, B Eslami-Mossallam, H Schiessel
About three quarters of our DNA is wrapped into nucleosomes: DNA spools with a protein core. It is well known that the affinity of a given DNA stretch to be incorporated into a nucleosome depends on the geometry and elasticity of the basepair sequence involved, causing the positioning of nucleosomes. Here we show that DNA elasticity can have a much deeper effect on nucleosomes than just their positioning: it affects their "identities". Employing a recently developed computational algorithm, the mutation Monte Carlo method, we design nucleosomes with surprising physical characteristics...
May 2017: Physical Review. E
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