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Chromatin structure regulation

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https://www.readbyqxmd.com/read/28088069/nuclear-pore-complexes-and-regulation-of-gene-expression
#1
REVIEW
Marcela Raices, Maximiliano A D'Angelo
Nuclear pore complexes (NPCs), are large multiprotein channels that penetrate the nuclear envelope connecting the nucleus to the cytoplasm. Accumulating evidence shows that besides their main role in regulating the exchange of molecules between these two compartments, NPCs and their components also play important transport-independent roles, including gene expression regulation, chromatin organization, DNA repair, RNA processing and quality control, and cell cycle control. Here, we will describe the recent findings about the role of these structures in the regulation of gene expression...
January 11, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28087711/ctcf-mediated-topological-boundaries-during-development-foster-appropriate-gene-regulation
#2
Varun Narendra, Milica Bulajić, Job Dekker, Esteban O Mazzoni, Danny Reinberg
The genome is organized into repeating topologically associated domains (TADs), each of which is spatially isolated from its neighbor by poorly understood boundary elements thought to be conserved across cell types. Here, we show that deletion of CTCF (CCCTC-binding factor)-binding sites at TAD and sub-TAD topological boundaries that form within the HoxA and HoxC clusters during differentiation not only disturbs local chromatin domain organization and regulatory interactions but also results in homeotic transformations typical of Hox gene misregulation...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28078514/the-molecular-basis-of-the-organization-of-repetitive-dna-containing-constitutive-heterochromatin-in-mammals
#3
REVIEW
Gohei Nishibuchi, Jérôme Déjardin
Constitutive heterochromatin is composed mainly of repetitive elements and represents the typical inert chromatin structure in eukaryotic cells. Approximately half of the mammalian genome is made of repeat sequences, such as satellite DNA, telomeric DNA, and transposable elements. As essential genes are not present in these regions, most of these repeat sequences were considered as junk DNA in the past. However, it is now clear that these regions are essential for chromosome stability and the silencing of neighboring genes...
January 11, 2017: Chromosome Research
https://www.readbyqxmd.com/read/28076955/post-translational-modifications-of-trypanosoma-cruzi-canonical-and-variant-histones
#4
Gisele F A Picchi, Vanessa Zulkievicz, Marco Aurelio Krieger, Nilson T Zanchin, Samuel Goldenberg, Lyris M F de Godoy
Chagas disease, caused by Trypanosoma cruzi, still affects millions of people around the world. No vaccines neither treatment for chronic Chagas disease are available, and chemotherapy for the acute phase is hindered by limited efficacy and severe side effects. The processes by which the parasite acquires infectivity and survives in different hosts involve tight regulation of gene expression, mainly post-transcriptionally. Nevertheless, chromatin structure/organization of trypanosomatids is similar to other eukaryotes, including histone variants and post-translational modifications...
January 11, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28076866/biophysically-motivated-regulatory-network-inference-progress-and-prospects
#5
Tarmo Äijö, Richard Bonneau
Thanks to the confluence of genomic technology and computational developments, the possibility of network inference methods that automatically learn large comprehensive models of cellular regulation is closer than ever. This perspective focuses on enumerating the elements of computational strategies that, when coupled to appropriate experimental designs, can lead to accurate large-scale models of chromatin state and transcriptional regulatory structure and dynamics. We highlight 4 research questions that require further investigation in order to make progress in network inference: (1) using overall constraints on network structure such as sparsity, (2) use of informative priors and data integration to constrain individual model parameters, (3) estimation of latent regulatory factor activity under varying cell conditions, and (4) new methods for learning and modeling regulatory factor interactions...
2016: Human Heredity
https://www.readbyqxmd.com/read/28074286/regulation-of-microtubule-nucleation-mediated-by-%C3%AE-tubulin-complexes
#6
REVIEW
Vadym Sulimenko, Zuzana Hájková, Anastasiya Klebanovych, Pavel Dráber
The microtubule cytoskeleton is critically important for spatio-temporal organization of eukaryotic cells. The nucleation of new microtubules is typically restricted to microtubule organizing centers (MTOCs) and requires γ-tubulin that assembles into multisubunit complexes of various sizes. γ-Tubulin ring complexes (TuRCs) are efficient microtubule nucleators and are associated with large number of targeting, activating and modulating proteins. γ-Tubulin-dependent nucleation of microtubules occurs both from canonical MTOCs, such as spindle pole bodies and centrosomes, and additional sites such as Golgi apparatus, nuclear envelope, plasma membrane-associated sites, chromatin and surface of pre-existing microtubules...
January 10, 2017: Protoplasma
https://www.readbyqxmd.com/read/28073943/kdm4b-jmjd2b-is-a-p53-target-gene-that-modulates-the-amplitude-of-p53-response-after-dna-damage
#7
Laura Castellini, Eui Jung Moon, Olga V Razorenova, Adam J Krieg, Rie von Eyben, Amato J Giaccia
The p53 tumor suppressor protein plays a critical role in orchestrating the genomic response to various stress signals by acting as a master transcriptional regulator. Differential gene activity is controlled by transcription factors but also dependent on the underlying chromatin structure, especially on covalent histone modifications. After screening different histone lysine methyltransferases and demethylases, we identified JMJD2B/KDM4B as a p53-inducible gene in response to DNA damage. p53 directly regulates JMJD2B gene expression by binding to a canonical p53-consensus motif in the JMJD2B promoter...
January 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28072526/type-i-dna-topoisomerases
#8
Giovanni Capranico, Jessica Marinello, Giovanni Chillemi
DNA topoisomerases constitute a large family of essential enzymes in all domains of life. Even though they share the general reaction chemistry and the ability to govern DNA topology and resolve strand entanglements during fundamental molecular processes, they are characterized by differences in structural organization, modes of enzymatic catalysis and biological functions. Moreover, hundreds of compounds are known to interfere with bacterial and/or eukaryotic enzymes, and some of them are effective drugs for the treatment of infectious diseases and cancers...
January 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28069354/bufadienolides-from-amphibians-a-promising-source-of-anticancer-prototypes-for-radical-innovation-apoptosis-triggering-and-na-k-atpase-inhibition
#9
REVIEW
Lívia Queiroz de Sousa, Kátia da Conceição Machado, Samara Ferreira de Carvalho Oliveira, Lidiane da Silva Araújo, Evaldo Dos Santos Monção-Filho, Ana Amélia de Carvalho Melo-Cavalcante, Gerardo Magela Vieira-Júnior, Paulo Michel Pinheiro Ferreira
Amphibians present pharmacologically active aliphatic, aromatic and heterocyclic molecules in their skin as defense against microorganisms, predators and infections, such as steroids, alkaloids, biogenic amines, guanidine derivatives, proteins and peptides. Based on the discovered bioactive potential of bufadienolides, this work reviewed the contribution of amphibians, especially from members of Bufonidae family, as source of new cytotoxic and antitumor molecules, highlighting the mechanisms responsible for such amazing biological potentialities...
January 6, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28069135/epigenetic-control-of-gene-expression-in-maize
#10
J Huang, J S Lynn, L Schulte, S Vendramin, K McGinnis
Epigenetic gene regulation is important for proper development and gene expression in eukaryotes. Maize has a large and complex genome that includes abundant repetitive sequences which are frequently silenced by epigenetic mechanisms, making it an ideal organism to study epigenetic gene regulation. Epigenetic modifications are chromosome-bound, heritable changes to the genome that do not affect the DNA sequence, and can include DNA methylation, histone modification, and RNA processing. Our appreciation and understanding of epigenetic regulation has grown with the field since its inception ∼65 years ago...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28069134/the-multifaceted-contributions-of-chromatin-to-hiv-1-integration-transcription-and-latency
#11
E De Crignis, T Mahmoudi
The capacity of the human immunodeficiency virus (HIV-1) to establish latent infections constitutes a major barrier to the development of a cure for HIV-1. In latent infection, replication competent HIV-1 provirus is integrated within the host genome but remains silent, masking the infected cells from the activity of the host immune response. Despite the progress in elucidating the molecular players that regulate HIV-1 gene expression, the mechanisms driving the establishment and maintenance of latency are still not fully understood...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28067802/stabilization-of-nucleosomes-by-histone-tails-and-by-fact-revealed-by-spfret-microscopy
#12
Maria E Valieva, Nadezhda S Gerasimova, Kseniya S Kudryashova, Anastasia L Kozlova, Mikhail P Kirpichnikov, Qi Hu, Maria Victoria Botuyan, Georges Mer, Alexey V Feofanov, Vasily M Studitsky
A correct chromatin structure is important for cell viability and is tightly regulated by numerous factors. Human protein complex FACT (facilitates chromatin transcription) is an essential factor involved in chromatin transcription and cancer development. Here FACT-dependent changes in the structure of single nucleosomes were studied with single-particle Förster resonance energy transfer (spFRET) microscopy using nucleosomes labeled with a donor-acceptor pair of fluorophores, which were attached to the adjacent gyres of DNA near the contact between H2A-H2B dimers...
January 6, 2017: Cancers
https://www.readbyqxmd.com/read/28065669/the-role-of-chromatin-structure-in-gene-regulation-of-the-human-malaria-parasite
#13
REVIEW
Gayani Batugedara, Xueqing M Lu, Evelien M Bunnik, Karine G Le Roch
The human malaria parasite, Plasmodium falciparum, depends on a coordinated regulation of gene expression for development and propagation within the human host. Recent developments suggest that gene regulation in the parasite is largely controlled by epigenetic mechanisms. Here, we discuss recent advancements contributing to our understanding of the mechanisms controlling gene regulation in the parasite, including nucleosome landscape, histone modifications, and nuclear architecture. In addition, various processes involved in regulation of parasite-specific genes and gene families are examined...
January 5, 2017: Trends in Parasitology
https://www.readbyqxmd.com/read/28064308/-structural-studies-of-chromatin-remodeling-factors
#14
O I Volokh, N I Derkacheva, V M Studitsky, O S Sokolova
Changes of chromatin structure require participation of chromatin remodeling factors (CRFs), which are ATP-dependent multisubunit complexes that change the structure of the nucleosome without covalently modifying its components. CRFs act together with other protein factors to regulate the extent of chromatin condensation. Four CRF families are currently distinguished based on their structural and biochemical characteristics: SWI/SNF, ISWI, Mi-2/CHD, and SWR/INO80. X-ray diffraction analysis and electron microscopy are the main methods to obtain structural information about macromolecules...
November 2016: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28062559/atrx-and-daxx-mechanisms-and-mutations
#15
Michael A Dyer, Zulekha A Qadeer, David Valle-Garcia, Emily Bernstein
Recent genome sequencing efforts in a variety of cancers have revealed mutations and/or structural alterations in ATRX and DAXX, which together encode a complex that deposits histone variant H3.3 into repetitive heterochromatin. These regions include retrotransposons, pericentric heterochromatin, and telomeres, the latter of which show deregulation in ATRX/DAXX-mutant tumors. Interestingly, ATRX and DAXX mutations are often found in pediatric tumors, suggesting a particular developmental context in which these mutations drive disease...
January 6, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28062403/mutated-chromatin-regulatory-factors-as-tumor-drivers-in-cancer
#16
REVIEW
Carl Koschmann, Felipe J Nunez, Flor Mendez, Jacqueline A Brosnan-Cashman, Alan K Meeker, Pedro R Lowenstein, Maria G Castro
Genes encoding proteins that regulate chromatin structure and DNA modifications [i.e., chromatin regulatory factors (CRF)] and genes encoding histone proteins harbor recurrent mutations in most human cancers. These mutations lead to modifications in tumor chromatin and DNA structure and an altered epigenetic state that contribute to tumorigenesis. Mutated CRFs have now been identified in most types of cancer and are increasingly regarded as novel therapeutic targets. In this review, we discuss DNA alterations in CRFs and how these influence tumor chromatin structure and function, which in turn leads to tumorigenesis...
January 6, 2017: Cancer Research
https://www.readbyqxmd.com/read/28061806/modular-combinatorial-binding-among-human-trans-acting-factors-reveals-direct-and-indirect-factor-binding
#17
Yuchun Guo, David K Gifford
BACKGROUND: The combinatorial binding of trans-acting factors (TFs) to the DNA is critical to the spatial and temporal specificity of gene regulation. For certain regulatory regions, more than one regulatory module (set of TFs that bind together) are combined to achieve context-specific gene regulation. However, previous approaches are limited to either pairwise TF co-association analysis or assuming that only one module is used in each regulatory region. RESULTS: We present a new computational approach that models the modular organization of TF combinatorial binding...
January 6, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28060558/the-connection-between-brg1-ctcf-and-topoisomerases-at-tad-boundaries
#18
A Rasim Barutcu, Jane B Lian, Janet L Stein, Gary S Stein, Anthony N Imbalzano
The eukaryotic genome is partitioned into topologically associating domains (TADs). Despite recent advances characterizing TADs and TAD boundaries, the organization of these structures is an important dimension of genome architecture and function that is not well understood. Recently, we demonstrated that knockdown of BRG1, an ATPase driving the chromatin remodeling activity of mammalian SWI/SNF enzymes, globally alters long-range genomic interactions and results in a reduction of TAD boundary strength. We provided evidence suggesting that this effect may be due to BRG1 affecting nucleosome occupancy around CTCF sites present at TAD boundaries...
January 6, 2017: Nucleus
https://www.readbyqxmd.com/read/28059867/influence-of-the-kdm4a-rs586339-polymorphism-on-overall-survival-in-asian-non-small-cell-lung-cancer-patients
#19
Charlie Marvalim, Jing Xiang Gimson Wong, Natalia Sutiman, Wan Teck Lim, Shao Weng Tan, Ravindran Kanesvaran, Quan Sing Ng, Amit Jain, Mei Kim Ang, Wan Ling Tan, Chee Keong Toh, Eng Huat Tan, Balram Chowbay
The critical role of lysine demethylase 4A (KDM4A), in regulating chromatin structure and consequently in driving cellular proliferation and oncogenesis has been the focus of recent studies. Non-small-cell lung cancer (NSCLC) patients with adenocarcinoma histology who were homozygous for KDM4A single nucleotide polymorphism (SNP)-A482 (rs586339) were recently shown to have significantly worse overall survival (OS) compared with patients with the wild-type or the heterozygous genotype at this locus (hazard ratio=1...
January 2, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28059076/structure-of-the-cohesin-loader-scc2
#20
William C H Chao, Yasuto Murayama, Sofía Muñoz, Andrew W Jones, Benjamin O Wade, Andrew G Purkiss, Xiao-Wen Hu, Aaron Borg, Ambrosius P Snijders, Frank Uhlmann, Martin R Singleton
The functions of cohesin are central to genome integrity, chromosome organization and transcription regulation through its prevention of premature sister-chromatid separation and the formation of DNA loops. The loading of cohesin onto chromatin depends on the Scc2-Scc4 complex; however, little is known about how it stimulates the cohesion-loading activity. Here we determine the large 'hook' structure of Scc2 responsible for catalysing cohesin loading. We identify key Scc2 surfaces that are crucial for cohesin loading in vivo...
January 6, 2017: Nature Communications
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