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https://www.readbyqxmd.com/read/28237796/permanganate-s1-nuclease-footprinting-reveals-non-b-dna-structures-with-regulatory-potential-across-a-mammalian-genome
#1
Fedor Kouzine, Damian Wojtowicz, Laura Baranello, Arito Yamane, Steevenson Nelson, Wolfgang Resch, Kyong-Rim Kieffer-Kwon, Craig J Benham, Rafael Casellas, Teresa M Przytycka, David Levens
DNA in cells is predominantly B-form double helix. Though certain DNA sequences in vitro may fold into other structures, such as triplex, left-handed Z form, or quadruplex DNA, the stability and prevalence of these structures in vivo are not known. Here, using computational analysis of sequence motifs, RNA polymerase II binding data, and genome-wide potassium permanganate-dependent nuclease footprinting data, we map thousands of putative non-B DNA sites at high resolution in mouse B cells. Computational analysis associates these non-B DNAs with particular structures and indicates that they form at locations compatible with an involvement in gene regulation...
February 17, 2017: Cell Systems
https://www.readbyqxmd.com/read/28235947/human-centromeric-cenp-a-chromatin-is-a-homotypic-octameric-nucleosome-at-all-cell-cycle-points
#2
Yael Nechemia-Arbely, Daniele Fachinetti, Karen H Miga, Nikolina Sekulic, Gautam V Soni, Dong Hyun Kim, Adeline K Wong, Ah Young Lee, Kristen Nguyen, Cees Dekker, Bing Ren, Ben E Black, Don W Cleveland
Chromatin assembled with centromere protein A (CENP-A) is the epigenetic mark of centromere identity. Using new reference models, we now identify sites of CENP-A and histone H3.1 binding within the megabase, α-satellite repeat-containing centromeres of 23 human chromosomes. The overwhelming majority (97%) of α-satellite DNA is found to be assembled with histone H3.1-containing nucleosomes with wrapped DNA termini. In both G1 and G2 cell cycle phases, the 2-4% of α-satellite assembled with CENP-A protects DNA lengths centered on 133 bp, consistent with octameric nucleosomes with DNA unwrapping at entry and exit...
February 24, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28235398/testis-specific-y-like-5-gene-expression-methylation-and-implications-for-drug-sensitivity-in-prostate-carcinoma
#3
Senthil R Kumar, Jeffrey N Bryan, Magda Esebua, James Amos-Landgraf, Tanner J May
BACKGROUND: TSPYL5, a putative tumor suppressor gene, belongs to the nucleosome assembly protein family. The chromosomal location of the TSPYL5 gene is 8Q22.1, and its exact role in prostate cancer etiology remains unclear. Further TSPYL5 gene and protein expression in prostate carcinoma cells and diseased tissues including its susceptibility for epigenetic silencing is unknown. Also, not known is the variation in TSPYL5 protein expression with regards to progression of prostatic carcinoma and its possible role in drug sensitivity...
February 24, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28224327/effects-of-in-vivo-and-in-vitro-administration-of-neuro-behcet-s-disease-igg
#4
Ece Erdağ, Ceren Şahin, Cem İsmail Küçükali, Sinem Bireller, Melike Küçükerden, Murat Kürtüncü, Recai Türkoğlu, Bedia Cakmakoglu, Erdem Tüzün, Feyza Arıcıoğlu
Antibodies directed against membrane antigens of neuronal axonal processes (neuropil) have been recently identified in neuro-Behcet's disease (NBD) patients. To delineate the potential pathogenic action of these antibodies, pooled sera from seven NBD patients with neuropil antibodies and seven healthy controls were divided into purified IgG and IgG-depleted serum (IgG-DS) fractions and each fraction was administered into lateral ventricles of rats. NBD IgG-injected rats showed reduced locomotor activity in the open field test as compared to NBD IgG-DS, healthy control IgG, healthy control IgG-DS and PBS injected rats (n = 10 for each group)...
February 21, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28223399/centromere-location-in-arabidopsis-is-unaltered-by-extreme-divergence-in-cenh3-protein-sequence
#5
Shamoni Maheshwari, Takayoshi Ishii, C Titus Brown, Andreas Houben, Luca Comai
During cell division, spindle fibers attach to chromosomes at centromeres. The DNA sequence at regional centromeres is fast evolving with no conserved genetic signature for centromere identity. Instead CENH3, a centromere-specific histone H3 variant, is the epigenetic signature that specifies centromere location across both plant and animal kingdoms. Paradoxically, CENH3 is also adaptively evolving. An ongoing question is whether CENH3 evolution is driven by a functional relationship with the underlying DNA sequence...
February 21, 2017: Genome Research
https://www.readbyqxmd.com/read/28222791/epig-statistical-inference-and-profiling-of-dna-methylation-from-whole-genome-bisulfite-sequencing-data
#6
Martin Vincent, Kamilla Mundbjerg, Jakob Skou Pedersen, Gangning Liang, Peter A Jones, Torben Falck Ørntoft, Karina Dalsgaard Sørensen, Carsten Wiuf
The study of epigenetic heterogeneity at the level of individual cells and in whole populations is the key to understanding cellular differentiation, organismal development, and the evolution of cancer. We develop a statistical method, epiG, to infer and differentiate between different epi-allelic haplotypes, annotated with CpG methylation status and DNA polymorphisms, from whole-genome bisulfite sequencing data, and nucleosome occupancy from NOMe-seq data. We demonstrate the capabilities of the method by inferring allele-specific methylation and nucleosome occupancy in cell lines, and colon and tumor samples, and by benchmarking the method against independent experimental data...
February 21, 2017: Genome Biology
https://www.readbyqxmd.com/read/28220502/variations-on-a-nucleosome-theme-the-structural-basis-of-centromere-function
#7
Olga Moreno-Moreno, Mònica Torras-Llort, Fernando Azorín
The centromere is a specialized chromosomal structure that dictates kinetochore assembly and, thus, is essential for accurate chromosome segregation. Centromere identity is determined epigenetically by the presence of a centromere-specific histone H3 variant, CENP-A, that replaces canonical H3 in centromeric chromatin. Here, we discuss recent work by Roulland et al. that identifies structural elements of the nucleosome as essential determinants of centromere function. In particular, CENP-A nucleosomes have flexible DNA ends due to the short αN helix of CENP-A...
February 21, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28218250/chromatin-remodeller-fun30-fft3-induces-nucleosome-disassembly-to-facilitate-rna-polymerase-ii-elongation
#8
Junwoo Lee, Eun Shik Choi, Hogyu David Seo, Keunsoo Kang, Joshua M Gilmore, Laurence Florens, Michael P Washburn, Joonho Choe, Jerry L Workman, Daeyoup Lee
Previous studies have revealed that nucleosomes impede elongation of RNA polymerase II (RNAPII). Recent observations suggest a role for ATP-dependent chromatin remodellers in modulating this process, but direct in vivo evidence for this is unknown. Here using fission yeast, we identify Fun30(Fft3) as a chromatin remodeller, which localizes at transcribing regions to promote RNAPII transcription. Fun30(Fft3) associates with RNAPII and collaborates with the histone chaperone, FACT, which facilitates RNAPII elongation through chromatin, to induce nucleosome disassembly at transcribing regions during RNAPII transcription...
February 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28213686/the-iswi-remodeler-in-plants-protein-complexes-biochemical-functions-and-developmental-roles
#9
REVIEW
Dongjie Li, Jie Liu, Wu Liu, Guang Li, Zhongnan Yang, Peng Qin, Lin Xu
Imitation Switch (ISWI) is a member of the ATP-dependent chromatin remodeling factor family, whose members move or restructure nucleosomes using energy derived from ATP hydrolysis. ISWI proteins are conserved in eukaryotes and usually form complexes with DDT (DNA-binding homeobox and different transcription factors)-domain proteins. Here, we review recent research on ISWI in the model plant Arabidopsis thaliana (AtISWI). AtISWI forms complexes with AtDDT-domain proteins, many of which have domain structures that differ from those of DDT-domain proteins in yeast and animals...
February 17, 2017: Chromosoma
https://www.readbyqxmd.com/read/28212748/systematic-investigation-of-transcription-factor-activity-in-the-context-of-chromatin-using-massively-parallel-binding-and-expression-assays
#10
Michal Levo, Tali Avnit-Sagi, Maya Lotan-Pompan, Yael Kalma, Adina Weinberger, Zohar Yakhini, Eran Segal
Precise gene expression patterns are established by transcription factor (TFs) binding to regulatory sequences. While these events occur in the context of chromatin, our understanding of how TF-nucleosome interplay affects gene expression is highly limited. Here, we present an assay for high-resolution measurements of both DNA occupancy and gene expression on large-scale libraries of systematically designed regulatory sequences. Our assay reveals occupancy patterns at the single-cell level. It provides an accurate quantification of the fraction of the population bound by a nucleosome and captures distinct, even adjacent, TF binding events...
February 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28212747/catalytic-independent-functions-of-parp-1-determine-sox2-pioneer-activity-at-intractable-genomic-loci
#11
Ziying Liu, W Lee Kraus
Pioneer transcription factors (TFs) function as genomic first responders, binding to inaccessible regions of chromatin to promote enhancer formation. The mechanism by which pioneer TFs gain access to chromatin remains an important unanswered question. Here we show that PARP-1, a nucleosome-binding protein, cooperates with intrinsic properties of the pioneer TF Sox2 to facilitate its binding to intractable genomic loci in embryonic stem cells. These actions of PARP-1 occur independently of its poly(ADP-ribosyl) transferase activity...
February 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28212744/parp1-and-sox2-an-unlikely-team-of-pioneers-to-conquer-the-nucleosome
#12
Guillaume Gaullier, Karolin Luger
In this issue of Molecular Cell, Liu and Kraus (2017) demonstrate that the pioneer transcription factor Sox2 requires PARP1 to bind to a subset of its recognition motifs, which are located within nucleosomes across the genome.
February 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28202543/nucleosome-like-ssdna-histone-octamer-complexes-and-the-implication-for-dna-double-strand-break-repair
#13
Nicholas L Adkins, Sarah G Swygert, Parminder Kaur, Hengyao Niu, Sergei A Grigoryev, Patrick Sung, Hong Wang, Craig L Peterson
Repair of DNA double strand breaks (DSBs) is key for maintenance of genome integrity. When DSBs are repaired by homologous recombination, DNA ends can undergo extensive processing, producing long stretches of single-stranded DNA (ssDNA). In vivo, DSB processing occurs in the context of chromatin, and studies indicate that histones may remain associated with processed DSBs. Here we demonstrate that histones are not evicted from ssDNA after in vitro chromatin resection. In addition, we reconstitute histone-ssDNA complexes (termed ssNucs) with ssDNA and recombinant histones and analyze these particles by a combination of native gel electrophoresis, sedimentation velocity, electron microscopy, and a recently developed electrostatic force microscopy technique, DREEM (Dual-Resonance-frequency-Enhanced Electrostatic force Microscopy)...
February 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28202515/systematic-in-vivo-inactivation-of-chromatin-regulating-enzymes-identifies-setd2-as-a-potent-tumor-suppressor-in-lung-adenocarcinoma
#14
David M Walter, Olivia S Venancio, Elizabeth L Buza, John W Tobias, Charuhas Deshpande, A Andrea Gudiel, Caroline Kim-Kiselak, Michelle Cicchini, Travis J Yates, David M Feldser
Chromatin modifying genes are frequently mutated in human lung adenocarcinoma, but the functional impact of these mutations on disease initiation and progression is not well understood. Using a CRISPR-based approach, we systematically inactivated three of the most commonly mutated chromatin regulatory genes in two KrasG12D-driven mouse models of lung adenocarcinoma to characterize the impact of their loss. Targeted inactivation of SWI/SNF nucleosome remodeling complex members Smarca4 (Brg1) or Arid1a had complex effects on lung adenocarcinoma initiation and progression...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28198434/jerantinine-a-induces-tumor-specific-cell-death-through-modulation-of-splicing-factor-3b-subunit-1-sf3b1
#15
Felicia Fei-Lei Chung, Perry Faith Tze Ming Tan, Vijay Joseph Raja, Boon-Shing Tan, Kuan-Hon Lim, Toh-Seok Kam, Ling-Wei Hii, Si Hoey Tan, Sze-Jia See, Yuen-Fen Tan, Li-Zhe Wong, Wai Keat Yam, Chun Wai Mai, Tracey D Bradshaw, Chee-Onn Leong
Precursor mRNA (pre-mRNA) splicing is catalyzed by a large ribonucleoprotein complex known as the spliceosome. Numerous studies have indicated that aberrant splicing patterns or mutations in spliceosome components, including the splicing factor 3b subunit 1 (SF3B1), are associated with hallmark cancer phenotypes. This has led to the identification and development of small molecules with spliceosome-modulating activity as potential anticancer agents. Jerantinine A (JA) is a novel indole alkaloid which displays potent anti-proliferative activities against human cancer cell lines by inhibiting tubulin polymerization and inducing G2/M cell cycle arrest...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28196481/nuctools-analysis-of-chromatin-feature-occupancy-profiles-from-high-throughput-sequencing-data
#16
Yevhen Vainshtein, Karsten Rippe, Vladimir B Teif
BACKGROUND: Biomedical applications of high-throughput sequencing methods generate a vast amount of data in which numerous chromatin features are mapped along the genome. The results are frequently analysed by creating binary data sets that link the presence/absence of a given feature to specific genomic loci. However, the nucleosome occupancy or chromatin accessibility landscape is essentially continuous. It is currently a challenge in the field to cope with continuous distributions of deep sequencing chromatin readouts and to integrate the different types of discrete chromatin features to reveal linkages between them...
February 14, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28191871/distinct-modes-of-smad2-chromatin-binding-and-remodeling-shape-the-transcriptional-response-to-nodal-activin-signaling
#17
Davide M Coda, Tessa Gaarenstroom, Philip East, Harshil Patel, Daniel S J Miller, Anna Lobley, Nik Matthews, Aengus Stewart, Caroline S Hill
NODAL/Activin signaling orchestrates key processes during embryonic development via SMAD2. How SMAD2 activates programs of gene expression that are modulated over time however, is not known. Here we delineate the sequence of events that occur from SMAD2 binding to transcriptional activation, and the mechanisms underlying them. NODAL/Activin signaling induces dramatic chromatin landscape changes, and a dynamic transcriptional network regulated by SMAD2, acting via multiple mechanisms. Crucially we have discovered two modes of SMAD2 binding...
February 13, 2017: ELife
https://www.readbyqxmd.com/read/28188921/mediator-swi-snf-and-saga-complexes-regulate-yap8-dependent-transcriptional-activation-of-acr2-in-response-to-arsenate
#18
Regina Andrade Menezes, Catarina Pimentel, Ana Rita Courelas Silva, Catarina Amaral, Jawad Merhej, Frédéric Devaux, Claudina Rodrigues-Pousada
Response to arsenic stress in Saccharomyces cerevisiae is orchestrated by the regulatory protein Yap8, which mediates transcriptional activation of ACR2 and ACR3. This study contributes to the state of art knowledge of the molecular mechanisms underlying yeast stress response to arsenate as it provides the genetic and biochemical evidences that Yap8, through cysteine residues 132, 137, and 274, is the sensor of presence of arsenate in the cytosol. Moreover, it is here reported for the first time the essential role of the Mediator complex in the transcriptional activation of ACR2 by Yap8...
February 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28188812/epigenetics-in-cancer-fundamentals-and-beyond
#19
REVIEW
Subhankar Biswas, C Mallikarjuna Rao
Activation of oncogenes or the deactivation of tumor suppressor genes has long been established as the fundamental mechanism leading towards carcinogenesis. Although this age old axiom is vastly accurate, thorough study over the last 15years has given us unprecedented information on the involvement of epigenetic in cancer. Various biochemical pathways that are essential towards tumorigenesis are regulated by the epigenetic phenomenons like remodeling of nucleosome by histone modifications, DNA methylation and miRNA mediated targeting of various genes...
February 8, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28188183/variants-of-the-sir4-coiled-coil-domain-improve-binding-to-sir3-for-heterochromatin-formation-in-saccharomyces-cerevisiae
#20
Anke Samel, Adam Rudner, Ann E Ehrenhofer-Murray
Heterochromatin formation in the yeast Saccharomyces cerevisiae is characterized by the assembly of the Silent Information Regulator (SIR) complex, which consists of the histone deacetylase Sir2 and the structural components Sir3 and Sir4 and binds to unmodified nucleosomes to provide gene silencing. Sir3 contains an AAA(+) ATPase-like domain, and mutations in an exposed loop on the surface of this domain abrogate Sir3 silencing function in vivo as well in vitro binding to the Sir2/ Sir4 subcomplex. Here, we found that the removal of a single methyl group in the C-terminal coiled-coil domain (mutation T1314S) of Sir4 was sufficient to restore silencing at the silent mating-type loci HMR and HML to a Sir3 version with a mutation in this loop...
February 10, 2017: G3: Genes—Genomes—Genetics
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