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https://www.readbyqxmd.com/read/27911399/tools-to-study-the-role-of-architectural-protein-hmgb1-in-the-processing-of-helix-distorting-site-specific-dna-interstrand-crosslinks
#1
Anirban Mukherjee, Karen M Vasquez
High mobility group box 1 (HMGB1) protein is a non-histone architectural protein that is involved in regulating many important functions in the genome, such as transcription, DNA replication, and DNA repair. HMGB1 binds to structurally distorted DNA with higher affinity than to canonical B-DNA. For example, we found that HMGB1 binds to DNA interstrand crosslinks (ICLs), which covalently link the two strands of the DNA, cause distortion of the helix, and if left unrepaired can cause cell death. Due to their cytotoxic potential, several ICL-inducing agents are currently used as chemotherapeutic agents in the clinic...
November 10, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911279/microrna-101-inhibits-proliferation-migration-and-invasion-of-human-glioblastoma-by-targeting-sox9
#2
Nan Liu, Lei Zhang, Zhen Wang, Yingduan Cheng, Pengxing Zhang, Xin Wang, Weihong Wen, Hongwei Yang, Hui Liu, Weilin Jin, Yongsheng Zhang, Yanyang Tu
Glioblastoma multiforme (GBM) is the most common primary malignant tumors originating in the brain parenchyma. At present, GBM patients have a poor prognosis despite the continuous progress in therapeutic technologies including surgery, radiotherapy, photodynamic therapy, and chemotherapy. Recent studies revealed that miR-101 was remarkably down-regulated in kinds of human cancers and was associated with aggressive tumor cell proliferation and stem cell self-renewal. Data also showed that miR-101 was down-regulated in primary glioma samples and cell lines, but the underlying molecular mechanism of the deregulation of miR-101 in glioma remained largely unknown...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911270/saha-and-or-mg132-reverse-the-aggressive-phenotypes-of-glioma-cells-an-in-vitro-and-vivo-study
#3
Xue-Feng Yang, Zhi-Juan Zhao, Jia-Jie Liu, Xiang-Hong Yang, Yang Gao, Shuang Zhao, Shuai Shi, Ke-Qiang Huang, Hua-Chuan Zheng
To elucidate the anti-tumor effects and molecular mechanisms of SAHA (a histone deacetylase inhibitor) and MG132 (a proteasome inhibitor) on the aggressive phenotypes of glioma cells, we treated U87 and U251 cells with SAHA or/and MG132, and detected phenotypes' assays with phenotype-related molecules examined. It was found that SAHA or/and MG132 treatment suppressed proliferation in both concentration- and time-dependent manners, inhibited energy metabolism, migration, invasion and lamellipodia formation, and induced G2 arrest and apoptosis in the glioma cells...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911260/population-scale-mapping-of-transposable-element-diversity-reveals-links-to-gene-regulation-and-epigenomic-variation
#4
Tim Stuart, Steven Eichten, Jonathan Cahn, Yuliya Karpievitch, Justin Borevitz, Ryan Lister
Variation in the presence or absence of transposable elements (TEs) is a major source of genetic variation between individuals. Here, we identified 23,095 TE presence/absence variants between 216 Arabidopsis accessions. Most TE variants were rare, and we find these rare variants associated with local extremes of gene expression and DNA methylation levels within the population. Of the common alleles identified, two thirds were not in linkage disequilibrium with nearby SNPs, implicating these variants as a source of novel genetic diversity...
December 2, 2016: ELife
https://www.readbyqxmd.com/read/27911230/bromodomain-inhibitors-and-cancer-therapy-from-structures-to-applications
#5
Montserrat Pérez-Salvia, Manel Esteller
Aberrations in the epigenetic landscape are a hallmark of cancer. Alterations in enzymes that are "writers", "erasers", or "readers" of histone modification marks are common. Bromodomains are "readers" that bind acetylated lysines in histone tails. Their most important function is the regulation of gene transcription by the recruitment of different molecular partners. Moreover, proteins containing bromodomains are also epigenetic regulators, although little is known about the specific function of these domains...
December 2, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27911222/the-histone-methyltransferases-set5-and-set1-have-overlapping-functions-in-gene-silencing-and-telomere-maintenance
#6
Meagan Jezek, Alison Gast, Grace Choi, Rushmie Kulkarni, Jeremiah Quijote, Andrew Graham-Yooll, DoHwan Park, Erin M Green
Genes adjacent to telomeres are subject to transcriptional repression mediated by an integrated set of chromatin modifying and remodeling factors. The telomeres of Saccharomyces cerevisiae have served as a model for dissecting the function of diverse chromatin proteins in gene silencing, and their study has revealed overlapping roles for many chromatin proteins in either promoting or antagonizing gene repression. The H3K4 methyltransferase Set1, which is commonly linked to transcriptional activation, has been implicated in telomere silencing...
December 2, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27911188/tuning-the-ribosome-the-influence-of-rrna-modification-on-eukaryotic-ribosome-biogenesis-and-function
#7
Katherine E Sloan, Ahmed S Warda, Sunny Sharma, Karl-Dieter Entian, Denis L J Lafontaine, Markus T Bohnsack
Ribosomal RNAs are extensively modified during their transcription and subsequent maturation in the nucleolus, nucleus and cytoplasm. RNA modifications, which are installed either by snoRNA-guided or by stand-alone enzymes, generally stabilise the structure of the ribosome. However, they also cluster at functionally important sites of the ribosome, such as the peptidyltransferase centre and the decoding site, where they facilitate efficient and accurate protein synthesis. The recent identification of sites of substoichiometric 2'-O-methylation and pseudouridylation has overturned the notion that all rRNA modifications are constitutively present on ribosomes, highlighting nucleotide modifications as an important source of ribosomal heterogeneity...
December 2, 2016: RNA Biology
https://www.readbyqxmd.com/read/27911186/rna-decay-evolution-and-the-testis
#8
Samantha H Jones, Miles Wilkinson
NMD is a highly conserved pathway that degrades specific subsets of RNAs. There is increasing evidence for roles of NMD in development. In this commentary, we focus on spermatogenesis, a process dramatically impeded upon loss or disruption of NMD. NMD requires strict regulation for normal spermatogenesis, as loss of a newly discovered NMD repressor, UPF3A, also causes spermatogenic defects, most prominently during meiosis. We discuss the unusual evolution of UPF3A, whose paralog, UPF3B, has the opposite biochemical function and acts in brain development...
December 2, 2016: RNA Biology
https://www.readbyqxmd.com/read/27910883/the-mechanism-of-transactivation-regulation-due-to-polymorphic-short-tandem-repeats-strs-using-igf1-promoter-as-a-model
#9
Holly Y Chen, Suk Ling Ma, Wei Huang, Lindan Ji, Vincent H K Leung, Honglin Jiang, Xiaoqiang Yao, Nelson L S Tang
Functional short tandem repeats (STR) are polymorphic in the population, and the number of repeats regulates the expression of nearby genes (known as expression STR, eSTR). STR in IGF1 promoter has been extensively studied for its association with IGF1 concentration in blood and various clinical traits and represents an important eSTR. We previously used an in-vitro luciferase reporter model to examine the interaction between STRs and SNPs in IGF1 promoter. Here, we further explored the mechanism how the number of repeats of the STR regulates gene transcription...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910850/the-guanine-nucleotide-exchange-factor-net1-facilitates-the-specification-of-dorsal-cell-fates-in-zebrafish-embryos-by-promoting-maternal-%C3%AE-catenin-activation
#10
Shi Wei, Miaomiao Dai, Zhaoting Liu, Yuanqing Ma, Hanqiao Shang, Yu Cao, Qiang Wang
Wnt/β-catenin signaling is essential for the initiation of dorsal-ventral patterning during vertebrate embryogenesis. Maternal β-catenin accumulates in dorsal marginal nuclei during cleavage stages, but its critical target genes essential for dorsalization are silent until mid-blastula transition (MBT). Here, we find that zebrafish net1, a guanine nucleotide exchange factor, is specifically expressed in dorsal marginal blastomeres after MBT, and acts as a zygotic factor to promote the specification of dorsal cell fates...
December 2, 2016: Cell Research
https://www.readbyqxmd.com/read/27910098/gata-3-specific-dnazyme-a-novel-approach-for-stratified-asthma-therapy
#11
REVIEW
Holger Garn, Harald Renz
It is now well established that type-2 immune mechanisms drive the inflammation in about 50% of asthma patients. The major cellular and molecular players regulating this important network have been identified. In terms of therapeutic intervention, cytokine and cytokine-receptor pathways have been given major attention, since these molecules are relatively easily accessible for a blockade through monoclonal antibodies, and a number of positive clinical results support this concept. However, targeting events controlling the type-2 immunity network upstream of selective cytokine pathways would be equally attractive...
December 2, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27910042/direct-cardiac-reprogramming-as-a-novel-therapeutic-strategy-for-treatment-of-myocardial-infarction
#12
Hong Ma, Li Wang, Jiandong Liu, Li Qian
Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds great promise as a novel therapy for the treatment of heart failure, a common and morbid disease that is usually caused by irreversible loss of functional cardiomyocytes (CMs). Recently, we and others showed that in a murine model of acute myocardial infarction, delivery of three transcription factors, Gata4, Mef2c, and Tbx5 converted endogenous cardiac fibroblasts into functional iCMs. These iCMs integrated electrically and mechanically with surrounding myocardium, resulting in a reduction in scar size and an improvement in heart function...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27909997/saururus-chinensis-baill-inhibits-proliferation-and-invasion-of-human-renal-cell-carcinoma-cells-through-inhibition-of-inhibitor-of-apoptosis-protein
#13
Yong Hyun Park, Jung-In Kim, Su Yeon Seo, Eunhye Lee, Hyeon Hoe Kim
OBJECTIVE: To investigate the inhibitory effect of Saururus chinensis Baill on cell viability, apoptosis, invasion capacity and the mechanism involved in human renal cell carcinoma (RCC) cells. METHODS: After treating A498 and ACHN cells with Saururus chinensis Baill extract (0, 25, 50 μg/mL), inhibitory effect of Saururus chinensis Baill were evaluated using tetrazolium salt-based colorimetric assay, flfl ow cytometry analysis, and in vitro Matrigel invasion assay, respectively...
December 1, 2016: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/27909897/nha2-is-expressed-in-distal-nephron-and-regulated-by-dietary-sodium
#14
Kalyan C Kondapalli, R Todd Alexander, Jennifer L Pluznick, Rajini Rao
Increased renal reabsorption of sodium is a significant risk factor in hypertension. An established clinical marker for essential hypertension is elevated sodium lithium countertransport (SLC) activity. NHA2 is a newly identified Na(+)(Li(+))/H(+) antiporter with potential genetic links to hypertension, which has been shown to mediate SLC activity and H(+)-coupled Na(+)(Li(+)) efflux in kidney-derived MDCK cells. To evaluate a putative role in sodium homeostasis, we determined the effect of dietary salt on NHA2...
December 1, 2016: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/27909734/klf4-inhibits-tumor-growth-and-metastasis-by-targeting-microrna-31-in-human-hepatocellular-carcinoma
#15
Chuan Tian, Shanshan Yao, Li Liu, Youcheng Ding, Qingwang Ye, Xiao Dong, Yong Gao, Ning Yang, Qi Li
MicroRNAs (miRNAs or miRs) are short, endogenous non-coding RNA molecules, demonstrating abnormal expression in cancer initiation and progression. In this study, we profiled 18 differentially regulated miRNAs, including miRNA‑31, using miRNA array. Kruppel (or Krüppel)-like factor 4 (Klf4) is a transcription factor and putative tumor suppressor. Both were found to be significantly downregulated in liver cancer tissues and cells. However, little is known about the correlation between Klf4 and miRNA‑31 in hepatocellular carcinoma (HCC)...
November 24, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27909441/apple-f-box-protein-mdmax2-regulates-plant-photomorphogenesis-and-stress-response
#16
Jian-Ping An, Rui Li, Feng-Jia Qu, Chun-Xiang You, Xiao-Fei Wang, Yu-Jin Hao
MAX2 (MORE AXILLARY GROWTH2) is involved in diverse physiological processes, including photomorphogenesis, the abiotic stress response, as well as karrikin and strigolactone signaling-mediated shoot branching. In this study, MdMAX2, an F-box protein that is a homolog of Arabidopsis MAX2, was identified and characterized. Overexpression of MdMAX2 in apple calli enhanced the accumulation of anthocyanin. Ectopic expression of MdMAX2 in Arabidopsis exhibited photomorphogenesis phenotypes, including increased anthocyanin content and decreased hypocotyl length...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27909439/the-a-allele-of-the-single-nucleotide-polymorphism-rs630923-creates-a-binding-site-for-mef2c-resulting-in-reduced-cxcr5-promoter-activity-in-b-cell-lymphoblastic-cell-lines
#17
Nikita A Mitkin, Alisa M Muratova, Anton M Schwartz, Dmitry V Kuprash
Chemokine receptor CXCR5 is highly expressed in B-cells and under normal conditions is involved in their migration to specific areas of secondary lymphoid organs. B-cells are known to play an important role in various autoimmune diseases including multiple sclerosis (MS) where areas of demyelinating lesions attract B-cells by overexpressing CXCL13, the CXCR5 ligand. In this study, we aimed to determine the functional significance of single-nucleotide polymorphism rs630923 (A/C), which is located in cxcr5 gene promoter, and its common allele is associated with increased risk of MS...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27909409/3-5-3-triiodo-l-thyronine-and-3-5-diiodo-l-thyronine-affected-metabolic-pathways-in-liver-of-ldl-receptor-deficient-mice
#18
Maria Moreno, Elena Silvestri, Maria Coppola, Ira J Goldberg, Li-Shin Huang, Anna M Salzano, Fulvio D'Angelo, Joel R Ehrenkranz, Fernando Goglia
3,5,3'-triiodo-L-thyronine (T3) and 3,5-diiodo-L-thyronine (T2), when administered to a model of familial hypercholesterolemia, i.e., low density lipoprotein receptor (LDLr)-knockout (Ldlr(-/-)) mice fed with a Western type diet (WTD), dramatically reduce circulating total and very low-density lipoprotein/LDL cholesterol with decreased liver apolipoprotein B (ApoB) production. The aim of the study was to highlight putative molecular mechanisms to manage cholesterol levels in the absence of LDLr. A comprehensive comparative profiling of changes in expression of soluble proteins in livers from Ldlr(-/-) mice treated with either T3 or T2 was performed...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27909249/mortalin-mediated-and-erk-controlled-targeting-of-hif-1%C3%AE-to-mitochondria-confers-resistance-to-apoptosis-under-hypoxia
#19
Ilias Mylonis, Maria Kourti, Martina Samiotaki, George Panayotou, George Simos
Hypoxia inducible factor-1 (HIF-1) is the main transcriptional activator of the cellular response to hypoxia and an important target of anticancer therapy. Phosphorylation by ERK stimulates the transcriptional activity of HIF-1α by inhibiting its CRM1-dependent nuclear export. Here, we demonstrate that phosphorylation by ERK also regulates the association of HIF-1α with a novel interaction partner identified as mortalin (GRP75) which mediates non-genomic involvement of HIF-1α in apoptosis. Mortalin binds specifically to HIF-1α lacking modification by ERK and their complex is localized outside the nucleus...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27909217/the-small-foxp1-isoform-predominantly-expressed-in-activated-b-cell-like-diffuse-large-b-cell-lymphoma-and-full-length-foxp1-exert-similar-oncogenic-and-transcriptional-activity-in-human-b-cells
#20
Martine van Keimpema, Leonie J Grüneberg, Esther J M Schilder-Tol, Monique E C M Oud, Esther Beuling, Paul J Hensbergen, Johann de Jong, Steven T Pals, Marcel Spaargaren
The forkhead transcription factor FOXP1 is generally regarded as an oncogene in activated B cell-like diffuse large B-cell lymphoma. Previous studies have suggested that a small isoform of FOXP1 (FOXP1-iso), rather than full-length FOXP1 (FOXP1-FL), may possess this oncogenic activity. Corroborating those studies, we here show that activated B cell-like diffuse large B-cell lymphoma cell-lines and primary activated B cell-like diffuse large B-cell lymphoma cells predominantly express FOXP1-iso and that the 5-end of the Foxp1 gene is a common insertion site in murine lymphomas in leukaemia virus- and transposon-mediated insertional mutagenesis screens...
December 1, 2016: Haematologica
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