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https://www.readbyqxmd.com/read/28526562/new-intracellular-activities-of-matrix-metalloproteinases-shine-in-the-moonlight
#1
REVIEW
Parker G Jobin, Georgina S Butler, ChristopherM Overall
Adaption of a single protein to perform multiple independent functions facilitates functional plasticity of the proteome allowing a limited number of protein-coding genes to perform a multitude of cellular processes. Multifunctionality is achievable by post-translational modifications and by modulating subcellular localization. Matrix metalloproteinases (MMPs), classically viewed as degraders of the extracellular matrix (ECM) responsible for matrix protein turnover, are more recently recognized as regulators of a range of extracellular bioactive molecules including chemokines, cytokines, and their binders...
May 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28526340/unfolding-the-pathogenesis-of-scleroderma-through-genomics-and-epigenomics
#2
REVIEW
Pei-Suen Tsou, Amr H Sawalha
With unknown etiology, scleroderma (SSc) is a multifaceted disease characterized by immune activation, vascular complications, and excessive fibrosis in internal organs. Genetic studies, including candidate gene association studies, genome-wide association studies, and whole-exome sequencing have supported the notion that while genetic susceptibility to SSc appears to be modest, SSc patients are genetically predisposed to this disease. The strongest genetic association for SSc lies within the MHC region, with loci in HLA-DRB1, HLA-DQB1, HLA-DPB1, and HLA-DOA1 being the most replicated...
May 16, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28525740/rnf8-and-ube2s-dependent-ubiquitin-lysine-11-linkage-modification-in-response-to-dna-damage
#3
Atanu Paul, Bin Wang
Ubiquitin modification of proteins plays pivotal roles in the cellular response to DNA damage. Given the complexity of ubiquitin conjugation due to the formation of poly-conjugates of different linkages, functional roles of linkage-specific ubiquitin modification at DNA damage sites are largely unclear. We identify that Lys11-linkage ubiquitin modification occurs at DNA damage sites in an ATM-dependent manner, and ubiquitin-modifying enzymes, including Ube2S E2-conjugating enzyme and RNF8 E3 ligase, are responsible for the assembly of Lys11-linkage conjugates on damaged chromatin, including histone H2A/H2AX...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28525736/a-flick-of-the-tail-keeps-the-circadian-clock-in-line
#4
Rajesh Narasimamurthy, David M Virshup
Circadian clocks signal and adapt to an ever-changing world by juggling a panoply of transcriptional and post-translational modifications. In this issue of Molecular Cell, Gustafson et al. (2017) report an additional requirement for accurate timekeeping, a cis/trans conformational flicker in the transcriptional activation domain of the core clock protein BMAL1.
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28524856/histone-variant-h3-3-orchestrates-neural-stem-cell-differentiation-in-the-developing-brain
#5
Wenlong Xia, Jianwei Jiao
During the brain development, the process of neural stem cells (NSCs) proliferation and differentiation is precisely regulated. The deficiency in the embryonic brain development will cause serious developmental disorders. Epigenetic modifications play critical roles in controlling proliferation and differentiation in different types of stem cells. Histone variants, as one of epigenetic regulators, have been reported to be associated with many bioprocesses. Among different variants, H3.3 is one of the important epigenetic regulators, but its role in embryonic NSCs remains unclear...
May 19, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28522548/a-multi-purpose-toolkit-to-enable-advanced-genome-engineering-in-plants
#6
Tomas Cermak, Shaun J Curtin, Javier Gil-Humanes, Radim Čegan, Thomas J Y Kono, Eva Konečná, Joseph J Belanto, Colby G Starker, Jade W Mathre, Rebecca L Greenstein, Daniel F Voytas
We report a comprehensive toolkit that enables targeted, specific modification of monocot and dicot genomes using a variety of genome engineering approaches. Our reagents, based on TALENs and the CRISPR/Cas9 system, are systematized for fast, modular cloning and accommodate diverse regulatory sequences to drive reagent expression. Vectors are optimized to create either single or multiple gene knockouts and large chromosomal deletions. Moreover, integration of geminivirus-based vectors enables precise gene editing through homologous recombination...
May 18, 2017: Plant Cell
https://www.readbyqxmd.com/read/28521626/experimental-evolution-of-resistance-against-bacillus-thuringiensis-in-the-insect-model-host-galleria-mellonella-results-in-epigenetic-modifications
#7
Krishnendu Mukherjee, Ekaterina Grizanova, Ekaterina Chertkova, Ruediger Lehmann, Ivan Dubovskiy, Andreas Vilcinskas
Epigenetic mechanisms have been proposed to translate environmental stimuli into heritable transgenerational phenotypic variations that can significantly influence natural selection. An intriguing example is exposure to pathogens, which imposes selection for host resistance. To test this hypothesis, we used larvae of the greater wax moth Galleria mellonella as model host to experimentally select for resistance to Bacillus thuringiensis (Bt), the most widely used bacterial agent for the biological control of pest insects...
May 19, 2017: Virulence
https://www.readbyqxmd.com/read/28521470/new-role-of-human-ribosomal-protein-s3-regulation-of-cell-cycle-via-phosphorylation-by-cyclin-dependent-kinase-2
#8
Se Hee Han, Ji Hyung Chung, Joon Kim, Key-Sun Kim, Ye Sun Han
Human ribosomal protein S3 (hRpS3) is a component of the 40S ribosomal subunit that associated in protein synthesis. hRpS3 has additional ribosomal functions such as DNA repair, transcription, metastasis, and apoptosis via interaction with numerous signaling molecules and has different modifications. Cyclin-dependent kinases (CDKs) are heterodimeric serine/threonine protein kinases that regulate cell cycle progression. Among its members, the Cdk1-cyclin B complex is known to control cell progression in the G2/M phase, while Cdk2-cyclin E/A complexes function in G1/S and S/G2 transition...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521392/phosphorylation-and-acetylation-modifications-of-foxo3a-independently-or-synergistically
#9
Xianwang Wang, Shujuan Hu, Lei Liu
Forkhead box class O 3a (FOXO3a) is a transcription factor that has emerged as being a tumor suppressor and longevity factor. The precise regulation of FOXO3a transactivation of target genes is achieved via post-translational modifications (PTMs) and specific protein-protein interactions. The multiple types of PTMs that FOXO3a undergoes, including phosphorylation, acetylation, methylation and ubiquitination, serve important roles in directing its subcellular localization and transcription activity, which are central to the integration of insulin/growth factor signaling and oxidative/nutrient stress signaling...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521327/epigenomics-pharmacoepigenomics-and-personalized-medicine-in-cervical-cancer
#10
Shama Prasada Kabekkodu, Sanjiban Chakrabarty, Supriti Ghosh, Angela Brand, Kapaettu Satyamoorthy
Epigenomics encompasses the study of genome-wide changes in DNA methylation, histone modifications and noncoding RNAs leading to altered transcription, chromatin structure, and posttranscription RNA processing, respectively, resulting in an altered rate of gene expression. The role of epigenetic modifications facilitating human diseases is well established. Previous studies have identified histone and cytosine code during normal and pathological conditions with special emphasis on how these modifications regulate transcriptional events...
May 19, 2017: Public Health Genomics
https://www.readbyqxmd.com/read/28521288/hypermethylation-of-ndn-promotes-cell-proliferation-by-activating-the-wnt-signaling-pathway-in-colorectal-cancer
#11
Yu-Han Hu, Qing Chen, Yan-Xia Lu, Jian-Ming Zhang, Chun Lin, Fan Zhang, Wen-Juan Zhang, Xiao-Min Li, Wei Zhang, Xue-Nong Li
The progression of CRC is a multistep process involving several genetic changes or epigenetic modifications. NDN is a member of the MAGE family, encoding a protein that generally suppresses cell proliferation and acting as a transcriptional repressor. Immunohistochemical staining revealed that the expression of NDN was significantly down-regulated in CRC tissues compared with normal tissues and the down-regulation of NDN in CRC could reflect the hypermethylation of the NDN promoter. Treatment of the CRC cell line SW480 with the demethylating agent 5-Aza-CdR restored the NDN expression level...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28521287/5azadc-treatment-upregulates-mir-375-level-and-represses-hpv16-e6-expression
#12
Adrien Morel, Aurélie Baguet, Jérôme Perrard, Caroline Demeret, Elise Jacquin, David Guenat, Christiane Mougin, Jean-Luc Prétet
High risk human papillomaviruses are the etiological agents of cervical cancer and HPV16 is the most oncogenic genotype. Immortalization and transformation of infected cells requires the overexpression of the two viral oncoproteins E6 and E7 following HPV DNA integration into the host cell genome. Integration often leads to the loss of the E2 open reading frame and the corresponding protein can no longer act as a transcriptional repressor on p97 promoter. Recently, it has been proposed that long control region methylation also contributes to the regulation of E6/E7 expression...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28521126/structural-and-functional-architecture-of-ampa-type-glutamate-receptors-and-their-auxiliary-proteins
#13
REVIEW
Ingo H Greger, Jake F Watson, Stuart G Cull-Candy
AMPA receptors (AMPARs) are tetrameric ion channels that together with other ionotropic glutamate receptors (iGluRs), the NMDA and kainate receptors, mediate a majority of excitatory neurotransmission in the central nervous system. Whereas NMDA receptors gate channels with slow kinetics, responsible primarily for generating long-term synaptic potentiation and depression, AMPARs are the main fast transduction elements at synapses and are critical for the expression of plasticity. The kinetic and conductance properties of AMPARs are laid down during their biogenesis and are regulated by post-transcriptional RNA editing, splice variation, post-translational modification, and subunit composition...
May 17, 2017: Neuron
https://www.readbyqxmd.com/read/28520954/h2b-ubiquitylation-and-the-histone-chaperone-asf1-cooperatively-mediate-the-formation-and-maintenance-of-heterochromatin-silencing
#14
Meng-Ying Wu, Chia-Yeh Lin, Hsin-Yi Tseng, Fei-Man Hsu, Pao-Yang Chen, Cheng-Fu Kao
Heterochromatin is a heritable form of gene repression, with critical roles in development and cell identity. Understanding how chromatin factors results in such repression is a fundamental question. Chromatin is assembled and disassembled during transcription, replication and repair by anti-silencing function 1 (Asf1), a highly conserved histone chaperone. Transcription and DNA replication are also affected by histone modifications that modify nucleosome dynamics, such as H2B ubiquitylation (H2Bub). We report here that H2Bub and Asf1 cooperatively promote transcriptional silencing at yeast telomeres and mating loci...
May 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28520934/the-smap1-2-proteins-of-the-crenarchaeon-sulfolobus-solfataricus-interact-with-the-exosome-and-stimulate-a-rich-tailing-of-transcripts
#15
Birgit Märtens, Linlin Hou, Fabian Amman, Michael T Wolfinger, Elena Evguenieva-Hackenberg, Udo Bläsi
The conserved Sm and Sm-like proteins are involved in different aspects of RNA metabolism. Here, we explored the interactome of SmAP1 and SmAP2 of the crenarchaeon Sulfolobus solfataricus (Sso) to shed light on their physiological function(s). Both, SmAP1 and SmAP2 co-purified with several proteins involved in RNA-processing/modification, translation and protein turnover as well as with components of the exosome involved in 3΄ to 5΄ degradation of RNA. In follow-up studies a direct interaction with the poly(A) binding and accessory exosomal subunit DnaG was demonstrated...
May 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28515491/the-emerging-field-of-epigenetics-in-neurodegeneration-and-neuroprotection
#16
REVIEW
Jee-Yeon Hwang, Kelly A Aromolaran, R Suzanne Zukin
Epigenetic mechanisms - including DNA methylation, histone post-translational modifications and changes in nucleosome positioning - regulate gene expression, cellular differentiation and development in almost all tissues, including the brain. In adulthood, changes in the epigenome are crucial for higher cognitive functions such as learning and memory. Striking new evidence implicates the dysregulation of epigenetic mechanisms in neurodegenerative disorders and diseases. Although these disorders differ in their underlying causes and pathophysiologies, many involve the dysregulation of restrictive element 1-silencing transcription factor (REST), which acts via epigenetic mechanisms to regulate gene expression...
May 18, 2017: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/28514649/widespread-mitotic-bookmarking-by-histone-marks-and-transcription-factors-in-pluripotent-stem-cells
#17
Yiyuan Liu, Bobbie Pelham-Webb, Dafne Campigli Di Giammartino, Jiexi Li, Daleum Kim, Katsuhiro Kita, Nestor Saiz, Vidur Garg, Ashley Doane, Paraskevi Giannakakou, Anna-Katerina Hadjantonakis, Olivier Elemento, Effie Apostolou
During mitosis, transcription is halted and many chromatin features are lost, posing a challenge for the continuity of cell identity, particularly in fast cycling stem cells, which constantly balance self-renewal with differentiation. Here we show that, in pluripotent stem cells, certain histone marks and stem cell regulators remain associated with specific genomic regions of mitotic chromatin, a phenomenon known as mitotic bookmarking. Enhancers of stem cell-related genes are bookmarked by both H3K27ac and the master regulators OCT4, SOX2, and KLF4, while promoters of housekeeping genes retain high levels of mitotic H3K27ac in a cell-type invariant manner...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28514170/discovery-of-novel-11-triazole-substituted-benzofuro-3-2-b-quinolone-derivatives-as-c-myc-g-quadruplex-specific-stabilizers-via-click-chemistry
#18
De-Ying Zeng, Guo-Tao Kuang, Shi-Ke Wang, Wang Peng, Shu-Ling Lin, Qi Zhang, Xiao-Xuan Su, Ming-Hao Hu, Honggen Wang, Jia-Heng Tan, Zhi-Shu Huang, Lian-Quan Gu, Tian-Miao Ou
The specificity of nucleic acids' binders is crucial for developing this kind of drugs, especially for novel G-quadruplexes' binders. Quindoline derivatives have been developed as G-quadruplex stabilizers with good interactive activities. In order to improve the selectivity and binding affinity of quindoline derivatives as c-myc G-quadruplex binding ligands, novel triazole containing benzofuroquinoline derivatives (T-BFQs) were designed and synthesized by using the 1,3-dipolar cycloaddition of a series of alkyne and azide building blocks...
May 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28513600/temporal-dynamics-of-gene-expression-and-histone-marks-at-the-arabidopsis-shoot-meristem-during-flowering
#19
Yuan You, Aneta Sawikowska, Manuela Neumann, David Posé, Giovanna Capovilla, Tobias Langenecker, Richard A Neher, Paweł Krajewski, Markus Schmid
Plants can produce organs throughout their entire life from pluripotent stem cells located at their growing tip, the shoot apical meristem (SAM). At the time of flowering, the SAM of Arabidopsis thaliana switches fate and starts producing flowers instead of leaves. Correct timing of flowering in part determines reproductive success, and is therefore under environmental and endogenous control. How epigenetic regulation contributes to the floral transition has eluded analysis so far, mostly because of the poor accessibility of the SAM...
May 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28512461/transcriptional-responses-to-pre-flowering-leaf-defoliation-in-grapevine-berry-from-different-growing-sites-years-and-genotypes
#20
Sara Zenoni, Silvia Dal Santo, Giovanni B Tornielli, Erica D'Incà, Ilaria Filippetti, Chiara Pastore, Gianluca Allegro, Oriana Silvestroni, Vania Lanari, Antonino Pisciotta, Rosario Di Lorenzo, Alberto Palliotti, Sergio Tombesi, Matteo Gatti, Stefano Poni
Leaf removal is a grapevine canopy management technique widely used to modify the source-sink balance and/or microclimate around berry clusters to optimize fruit composition. In general, the removal of basal leaves before flowering reduces fruit set, hence achieving looser clusters, and improves grape composition since yield is generally curtailed more than proportionally to leaf area itself. Albeit responses to this practice seem quite consistent, overall vine performance is affected by genotype, environmental conditions, and severity of treatment...
2017: Frontiers in Plant Science
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