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Chromatin modulation

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https://www.readbyqxmd.com/read/29224136/a-summary-of-the-biological-processes-disease-associated-changes-and-clinical-applications-of-dna-methylation
#1
Gitte Brinch Andersen, Jörg Tost
DNA methylation at cytosines followed by guanines, CpGs, forms one of the multiple layers of epigenetic mechanisms controlling and modulating gene expression through chromatin structure. It closely interacts with histone modifications and chromatin remodeling complexes to form the local genomic and higher-order chromatin landscape. DNA methylation is essential for proper mammalian development, crucial for imprinting and plays a role in maintaining genomic stability. DNA methylation patterns are susceptible to change in response to environmental stimuli such as diet or toxins, whereby the epigenome seems to be most vulnerable during early life...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29222611/kiwifruit-svp2-controls-developmental-and-drought-stress-pathways
#2
Rongmei Wu, Tianchi Wang, Ben A W Warren, Susan J Thomson, Andrew C Allan, Richard C Macknight, Erika Varkonyi-Gasic
Genome-wide targets of Actinidia chinensis SVP2 confirm roles in ABA- and dehydration-mediated growth repression and reveal a conservation in mechanism of action between SVP genes of taxonomically distant Arabidopsis and a woody perennial kiwifruit. The molecular mechanisms underlying growth and dormancy in woody perennials are largely unknown. In Arabidopsis, the MADS-box transcription factor SHORT VEGETATIVE PHASE (SVP) plays a key role in the progression from vegetative to floral development, and in woody perennials SVP-like genes are also proposed to be involved in controlling dormancy...
December 8, 2017: Plant Molecular Biology
https://www.readbyqxmd.com/read/29221727/epigenetic-mechanisms-in-developmental-neurotoxicity
#3
REVIEW
M Raciti, S Ceccatelli
The constant interplay between environment (including both exogenous and endogenous factors) and epigenome (defined as the combination of chromatin, its covalent modifications and noncoding RNAs) triggers epigenetic events that, by modulating gene expression, capture information about changes in the environment. In this mini review, we will focus on the neurodevelopmental implications of exposure to adverse prenatal milieu with emphasis on mechanistic and functional aspects. Several neurotoxic insults have been shown to affect epigenetics with negative consequences on the development of the nervous system; among them are methylmercury, lead, arsenic and cadmium, as well as excess of glucocorticoids...
December 5, 2017: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/29220653/a-poly-adp-ribose-trigger-releases-the-auto-inhibition-of-a-chromatin-remodeling-oncogene
#4
Hari R Singh, Aurelio P Nardozza, Ingvar R Möller, Gunnar Knobloch, Hans A V Kistemaker, Markus Hassler, Nadine Harrer, Charlotte Blessing, Sebastian Eustermann, Christiane Kotthoff, Sébastien Huet, Felix Mueller-Planitz, Dmitri V Filippov, Gyula Timinszky, Kasper D Rand, Andreas G Ladurner
DNA damage triggers chromatin remodeling by mechanisms that are poorly understood. The oncogene and chromatin remodeler ALC1/CHD1L massively decompacts chromatin in vivo yet is inactive prior to DNA-damage-mediated PARP1 induction. We show that the interaction of the ALC1 macrodomain with the ATPase module mediates auto-inhibition. PARP1 activation suppresses this inhibitory interaction. Crucially, release from auto-inhibition requires a poly-ADP-ribose (PAR) binding macrodomain. We identify tri-ADP-ribose as a potent PAR-mimic and synthetic allosteric effector that abrogates ATPase-macrodomain interactions, promotes an ungated conformation, and activates the remodeler's ATPase...
December 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29216371/fission-yeast-ccq1-is-a-modulator-of-telomerase-activity
#5
Christine A Armstrong, Vera Moiseeva, Laura C Collopy, Siân R Pearson, Tomalika R Ullah, Shidong T Xi, Jennifer Martin, Shaan Subramaniam, Sara Marelli, Hanna Amelina, Kazunori Tomita
Shelterin, the telomeric protein complex, plays a crucial role in telomere homeostasis. In fission yeast, telomerase is recruited to chromosome ends by the shelterin component Tpz1 and its binding partner Ccq1, where telomerase binds to the 3' overhang to add telomeric repeats. Recruitment is initiated by the interaction of Ccq1 with the telomerase subunit Est1. However, how telomerase is released following elongation remains to be established. Here, we show that Ccq1 also has a role in the suppression of telomere elongation, when coupled with the Clr4 histone H3 methyl-transferase complex and the Clr3 histone deacetylase and nucleosome remodelling complex, SHREC...
December 4, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29215703/design-synthesis-and-characterization-of-%C3%AE-%C3%AE-unsaturated-carboxylic-acid-and-its-urea-based-derivatives-that-explores-novel-epigenetic-modulators-in-human-non-small-cell-lung-cancer-a549-cell-line
#6
Anusha Chidambaram, S H Kavya, Ramesh Kumar Chidambaram, Rajasekaran Subbiah, John Marshal Jayaraj, Karthikeyan Muthusamy, Ravikumar Vilwanathan
Histone deacetylase inhibitors (HDACi) are a small molecule chemotherapeutics that target the chromatin remodeling through the regulation of histone and non-histone proteins. These inhibitors directed against HDAC enzymes have become an important therapeutic tool in oncology; consequently, scientific efforts have fortified the quest for newer and novel HDACi, which forces the design of structurally innovative HDACi. Various urea containing compounds exhibited admirable anticancer activity. On the basis of these observations, we design and synthesize HDAC specific blocker molecules which are specifically besieged towards class I, class II and class IV HDAC isoforms to enhance the structural assortment for HDACi...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29212285/bancr-a-novel-oncogenic-long-non-coding-rna-in-human-cancers
#7
REVIEW
Yifan Zou, Jianfa Li, Yincong Chen, Huizhong Xiao, Fuyou Zhang, Dan Yu, Kewang Luo
Long non-coding RNAs account for large proportion of non-coding transcripts in human genomes. Though they lack of open reading framework and cannot encode protein, they can control endogenous gene expression though regulating cell life activities. They serve as transcriptional modulator, posttranscriptional processor, chromatin remodeler and splicing regulator during the process of gene modification. Moreover, long non-coding RNAs were regarded as potential tumor markers for cancer diagnosis and prognosis. BANCR was identified as a cancer-promoting long non-coding RNA in melanoma tissues...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29211718/pirna-mediated-regulation-of-transposon-alternative-splicing-in-the-soma-and-germ-line
#8
Felipe Karam Teixeira, Martyna Okuniewska, Colin D Malone, Rémi-Xavier Coux, Donald C Rio, Ruth Lehmann
Transposable elements can drive genome evolution, but their enhanced activity is detrimental to the host and therefore must be tightly regulated. The Piwi-interacting small RNA (piRNA) pathway is vital for the regulation of transposable elements, by inducing transcriptional silencing or post-transcriptional decay of mRNAs. Here we show that piRNAs and piRNA biogenesis components regulate precursor mRNA splicing of P-transposable element transcripts in vivo, leading to the production of the non-transposase-encoding mature mRNA isoform in Drosophila germ cells...
December 6, 2017: Nature
https://www.readbyqxmd.com/read/29208640/shaping-chromatin-in-the-nucleus-the-bricks-and-the-architects
#9
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/29208466/chetomin-induces-apoptosis-in-human-triple-negative-breast-cancer-cells-by-promoting-calcium-overload-and-mitochondrial-dysfunction
#10
Jayant Dewangan, Sonal Srivastava, Sakshi Mishra, Prabhash Kumar Pandey, Aman Divakar, Srikanta Kumar Rath
Human triple-negative breast cancer (TNBC) is poorly diagnosed and unresponsive to conventional hormone therapy. Chetomin (CHET), a fungal metabolite synthesized by Chaetomium cochliodes, has been reported as a promising anticancer and antiangiogenic agent but the complete molecular mechanism of its anticancer potential remains to be elucidated. In our study, we explored the anti-neoplastic action of CHET on TNBC cells. Cytotoxicity studies were performed in human TNBC cells viz. MDA-MB-231 and MDA-MB-468 cells by Sulforhodamine B assay...
December 2, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29206861/preparative-two-step-purification-of-recombinant-h1-0-linker-histone-and-its-domains
#11
Nives Ivic, Silvija Bilokapic, Mario Halic
H1 linker histones are small basic proteins that have a key role in the formation and maintenance of higher-order chromatin structures. Additionally, many examples have shown that linker histones play an important role in gene regulation, modulated by their various subtypes and posttranslational modifications. Obtaining high amounts of very pure linker histones, especially for efficient antibody production, remains a demanding and challenging procedure. Here we present an easy and fast method to purify human linker histone H1...
2017: PloS One
https://www.readbyqxmd.com/read/29206651/novel-therapeutic-strategies-and-targets-in-advanced-uveal-melanoma
#12
Vivian Chua, Andrew E Aplin
PURPOSE OF REVIEW: Currently, there are no U.S. Food and Drug Administration-approved or effective treatment options for advanced-stage uveal melanoma. In this article, we focus on therapeutic targets in pathways/mechanisms associated with common mutations in uveal melanoma. We review the challenges associated with targeting of these pathways and novel treatment strategies. RECENT FINDINGS: Common mutations that promote uveal melanoma initiation and progression include alterations in G protein subunit alpha q/11 (GNAQ/GNA11) and breast cancer gene 1-associated protein 1 (BAP1)...
December 4, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29206173/histone-macroh2a1-a-chromatin-point-of-intersection-between-fasting-senescence-and-cellular-regeneration
#13
REVIEW
Oriana Lo Re, Manlio Vinciguerra
Histone variants confer chromatin unique properties. They have specific genomic distribution, regulated by specific deposition and removal machineries. Histone variants, mostly of canonical histones H2A, H2B and H3, have important roles in early embryonic development, in lineage commitment of stem cells, in the converse process of somatic cell reprogramming to pluripotency and, in some cases, in the modulation of animal aging and life span. MacroH2A1 is a variant of histone H2A, present in two alternatively exon-spliced isoforms macroH2A1...
December 5, 2017: Genes
https://www.readbyqxmd.com/read/29203878/atm-and-cdk2-control-chromatin-remodeler-csb-to-inhibit-rif1-in-dsb-repair-pathway-choice
#14
Nicole L Batenburg, John R Walker, Sylvie M Noordermeer, Nathalie Moatti, Daniel Durocher, Xu-Dong Zhu
CSB, a member of the SWI2/SNF2 superfamily, is implicated in DNA double-strand break (DSB) repair. However, how it regulates this repair process is poorly understood. Here we uncover that CSB interacts via its newly identified winged helix domain with RIF1, an effector of 53BP1, and that this interaction mediates CSB recruitment to DSBs in S phase. At DSBs, CSB remodels chromatin by evicting histones, which limits RIF1 and its effector MAD2L2 but promotes BRCA1 accumulation. The chromatin remodeling activity of CSB requires not only damage-induced phosphorylation on S10 by ATM but also cell cycle-dependent phosphorylation on S158 by cyclin A-CDK2...
December 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/29203199/overexpression-of-oct4-induced-by-modulation-of-histone-marks-plays-crucial-role-in-breast-cancer-progression
#15
Swayamsiddha Kar, Samir Kumar Patra
OCT4 is known as the gatekeeper of pluripotent embryonic state as it is responsible for maintenance of pluripotency via self-renewal of embryonic stem cells and acquisition of induced pluripotency via somatic cell reprogramming. OCT4 is responsible for oncogenic transformation by disrupting pre-scheduled differentiation programs and in general, favoring evolution of cancer cells into a more aggressive cancer stem cell phenotype. In this study, we have investigated in details, the epigenetic regulatory mechanisms responsible for over-expression and subsequent aberrant function of OCT4 in breast cancer...
December 1, 2017: Gene
https://www.readbyqxmd.com/read/29202635/the-coupled-effect-of-nucleosome-organization-on-gene-transcription-level-and-transcriptional-plasticity
#16
Jian Chen, EnLi, Jinsheng Lai
Nucleosomes are the fundamental units of eukaryotic chromatin and can modulate the DNA accessibility for transcriptional regulatory elements. Many studies have demonstrated the effect of nucleosome organization on gene transcription level and transcriptional plasticity upon different conditions. Our recent study showed that nucleosome organization also plays an important role in modulating the plasticity of gene transcriptional status in maize. Here, we integrated our findings with previous studies on the role of nucleosome organization in regulation of gene transcription...
December 5, 2017: Nucleus
https://www.readbyqxmd.com/read/29197138/testicular-orphan-receptor-4-promotes-tumor-progression-and-implies-poor-survival-through-akt3-regulation-in-seminoma
#17
Yuanlei Chen, Jieyang Lu, Liqun Xia, Dingwei Xue, Xiaoming Yu, Danyang Shen, Liwei Xu, Gonghui Li
Seminoma is recognized as the most common testicular germ cell tumor which mainly occurs in the 15-35-year-old young men worldwide. Early studies have indicated that testicular nuclear receptor 4 (TR4) firstly cloned from testis is involved in the invasion and metastasis of several human tumors, however, little attention is paid to the function of TR4 in Seminoma. Our Immunohistochemical (IHC) staining results showed that patients who underwent advanced stage tended to higher expression of TR4. Importantly, there was a significant association between elevated TR4 expression and reduced Overall Survival in seminoma patients...
December 2, 2017: Cancer Science
https://www.readbyqxmd.com/read/29194587/genetic-association-of-molecular-traits-a-help-to-identify-causative-variants-in-complex-diseases
#18
REVIEW
C Vandiedonck
In the past 15 years, major progresses have been made in the understanding of the genetic basis of regulation of gene expression. These new insights have revolutionized our approach to resolve the genetic variation underlying complex diseases. Gene transcript levels were the first expression phenotypes that were studied. They are heritable and therefore amenable to genome-wide association studies (GWAS). The genetic variants that modulate them are called expression quantitative trait loci (eQTL). Their study has been extended to other molecular quantitative trait loci (molQTL) that regulate gene expression at the various levels, from chromatin state to cellular responses...
December 1, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/29192133/synthetic-transcription-elongation-factors-license-transcription-across-repressive-chromatin
#19
Graham S Erwin, Matthew P Grieshop, Asfa Ali, Jun Qi, Matthew Lawlor, Deepak Kumar, Istaq Ahmad, Anna McNally, Natalia Teider, Katie Worringer, Rajeev Sivasankaran, Deeba N Syed, Asuka Eguchi, Md Ashraf, Justin Jeffery, Mousheng Xu, Paul M C Park, Hasan Mukhtar, Achal K Srivastava, Mohammed Faruq, James E Bradner, Aseem Z Ansari
Releasing a paused RNA polymerase II into productive elongation is tightly-regulated, especially at genes that impact human development and disease. To exert control over this rate-limiting step, we designed sequence-specific synthetic transcription elongation factors (Syn-TEFs). These molecules are composed of programmable DNA-binding ligands flexibly tethered to a small molecule that engages the transcription elongation machinery. By limiting activity to targeted loci, Syn-TEFs convert constituent modules from broad-spectrum inhibitors of transcription into gene-specific stimulators...
November 30, 2017: Science
https://www.readbyqxmd.com/read/29187597/emerging-roles-of-transcriptional-enhancers-in-chromatin-looping-and-promoter-proximal-pausing-of-rna-polymerase-ii
#20
Huan Meng, Blaine Bartholomew
Initiation and regulation of transcription by RNA polymerase II (RNAPII) in eukaryotes relies upon the control elements of promoters and enhancers. Promoters and enhancers share common architectures and functions in similar ways. The prevailing view is functional promoters and enhancers can initiate bidirectional transcription. With the acceleration of recent genome-wide studies of regulated transcription, it has become clear that transcriptional enhancers in mammalian genomes are major sources of pervasive non-coding RNA transcription...
November 29, 2017: Journal of Biological Chemistry
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