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Transcriptional regulation

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https://www.readbyqxmd.com/read/29236325/aml1-eto-trans-activates-c-kit-expression-through-the-long-range-interaction-between-promoter-and-intronic-enhancer
#1
Ying Tian, Genjie Wang, Qingzhu Hu, Xichun Xiao, Shuxia Chen
The AML1/ETO onco-fusion protein is crucial for the genesis of t(8;21) acute myeloid leukemia (AML) and is well documented as a transcriptional repressor through dominant-negative effect. However, little is known about the transactivation mechanism of AML1/ETO. Through large cohort of patient's expression level data analysis and a series of experimental validation, we report here that AML1/ETO transactivates c-KIT expression through directly binding to and mediating the long-range interaction between the promoter and intronic enhancer regions of c-KIT...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29236308/database-of-transcription-factors-in-lung-cancer-dbtflc-a-novel-resource-for-exploring-transcription-factors-associated-with-lung-cancer
#2
A Thabitha, Ameya Athul Dravid, Riya Tripathi, S Sajitha Lulu
Lung cancer is considered as the most prevalent form of cancer and it is found to be frequent cause of cancer related death. Even though, approved molecular targeted therapies other than chemotherapy are currently unavailable, the mechanism of pathogenesis in lung cancer remains still unclear. Transcription factors (TFs) play a critical role in cancer cell processes, such as cell proliferation, apoptosis, migration, and regulate gene expression. Thus, the identification and characterization of transcription factors involved in lung cancer would provide valuable information for further elucidation of the mechanism(s) underlying pathogenesis and the identification of potential therapeutic target types, which are critical for the development of therapeutic strategies...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29236306/rs4705342-polymorphism-is-involved-in-the-tumorigenesis-of-hbv-positive-hcc-by-altering-the-binding-affinity-of-hbv-induced-nf-kb-with-the-promoter-region-of-microrna-143
#3
Yin Xiuli, Sun Shiying, Zhao Junyan, Yang Jing, Lei Xiaofei, Xu Changqing, Li Kun
BACKGROUND: The objective of this study was to explore the role of rs4705342 located in the miR-143 promoter in relation to the control of HBV positive HCC and the underlying molecular mechanism. METHOD: A luciferase assay was performed to explore the factors which influenced miR-143 transcription activity and the target gene of miR-143. This would further be confirmed by ChIP assay. Western-blot and real-time PCR were performed to identify the relationship between miR-143 and ORP8...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29236292/a-novel-report-of-mir-4301-induces-cell-apoptosis-by-negatively-regulating-drd2-expression-in-human-breast-cancer-cells
#4
Naghmeh Gholipour, Anna Ohradanova-Repic, Ghasem Ahangari
BACKGROUND: In several cancers, microRNA (miRNAs) play vital roles in tumour initiation, drug resistance and metastasis. The aim of this study was to examine the expression levels of miR-4301 in human breast cancer and investigate whether its potential roles involved targeting Dopamine receptor D2 (DRD2). METHODS: Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was also used to examine the expression levels of miR-4301 in human breast cancer cell lines MDA-MB-231, MCF-7 and SKBR3...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29236291/dysregulation-of-mirna-biogenesis-machinery-and-mirna-rna-ratio-in-skeletal-muscle-of-als-mice
#5
Aaron P Russell, Lobna Ghobrial, Shyuan Ngo, Justin Yerbury, Evelyn Zacharewicz, Roger Chung, Séverine Lamon
INTRODUCTION: The pathology of amyotrophic lateral sclerosis (ALS) is associated with impaired RNA processing and miRNA dysregulation. Here we investigate the regulation of the members of the miRNA biogenesis pathways and total miRNA levels at different stages of the disease. METHODS: Muscle, brain and spinal cord tissue were obtained from pre-symptomatic, symptomatic and end-stage SOD1G93A mice. miRNA and transcript levels were measured by qPCR. RESULTS: As the diseases progresses, several genes involved in miRNA biogenesis as well as the miRNA/total RNA ratio increased in the tibialis anterior muscle, but not in the soleus or in neural tissue...
December 13, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/29236262/studying-nonsense-mediated-mrna-decay-in-mammalian-cells-using-a-multicolored-bioluminescence-based-reporter-system
#6
Andrew Nickless, Zhongsheng You
The nonsense-mediated mRNA decay (NMD) pathway degrades aberrant transcripts containing premature translation termination codons (PTCs) and also regulates the levels of many normal mRNAs containing NMD-inducing features. The activity of this pathway varies considerably in different cell types and can change in response to developmental and environmental cues. Modulating NMD activity represents a potential therapeutic avenue for certain genetic disorders and cancers. Simple reporter systems capable of faithfully assessing NMD activity in mammalian cells greatly facilitate both basic and translational research on NMD...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29236261/reactivation-assay-to-identify-direct-targets-of-the-nonsense-mediated-mrna-decay-pathway-in-drosophila
#7
Jonathan O Nelson, Mark M Metzstein
Transcriptome analysis provides a snapshot of cellular gene expression and is used to determine how cells and organisms respond to genetic or environmental changes. Identifying the transcripts whose expression levels are regulated directly by the manipulation being examined from those whose expression changes as a secondary cause from the primary changes requires additional analyses. Here we present a technique used to distinguish direct targets of the nonsense-mediated mRNA decay (NMD) pathway in Drosophila from secondary gene expression effects caused by loss of this pathway...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29236260/generation-of-cell-lines-stably-expressing-a-fluorescent-reporter-of-nonsense-mediated-mrna-decay-activity
#8
Nadezhda M Markina, Anton P Pereverzev, Dmitry B Staroverov, Konstantin A Lukyanov, Nadya G Gurskaya
Nonsense-mediated mRNA decay (NMD) is a mechanism of mRNA surveillance ubiquitous among eukaryotes. Importantly, NMD not only removes aberrant transcripts with premature stop codons, but also regulates expression of many normal genes. A recently introduced dual-color fluorescent protein-based reporter enables analysis of NMD activity in live cells. In this chapter we describe the method to generate stable transgenic cell lines expressing the splicing-dependent NMD reporter using consecutive steps of lentivirus transduction and Tol2 transposition...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29236259/identifying-cellular-nonsense-mediated-mrna-decay-nmd-targets-immunoprecipitation-of-phosphorylated-upf1-followed-by-rna-sequencing-p-upf1-rip-seq
#9
Tatsuaki Kurosaki, Mainul Hoque, Lynne E Maquat
Recent progress in the technology of transcriptome-wide high-throughput sequencing has revealed that nonsense-mediated mRNA decay (NMD) targets ~10% of physiologic transcripts for the purpose of tuning gene expression in response to various environmental conditions. Regardless of the eukaryote studied, NMD requires the ATP-dependent RNA helicase upframeshift 1 (UPF1). It was initially thought that cellular NMD targets could be defined by their binding to steady-state UPF1, which is largely hypophosphorylated...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29236258/using-tet-off-cells-and-rnai-knockdown-to-assay-mrna-decay
#10
Thomas D Baird, J Robert Hogg
Cellular mRNA levels are determined by the competing forces of transcription and decay. A wide array of cellular mRNA decay pathways carry out RNA turnover either on a constitutive basis or in response to changing cellular conditions. Here, we outline a method to investigate mRNA decay that employs RNAi knockdown of known or putative decay factors in commercially available Tet-off cell systems. Reporter mRNAs of interest are expressed under the control of a tetracycline-regulated promoter, allowing pulse-chase mRNA decay assays to be conducted...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29236199/caspase-cleavage-of-transcription-factor-sp1-enhances-apoptosis
#11
Behzad Torabi, Samuel Flashner, Kate Beishline, Aislinn Sowash, Kelly Donovan, Garrett Bassett, Jane Azizkhan-Clifford
Sp1 is a ubiquitous transcription factor that regulates many genes involved in apoptosis and senescence. Sp1 also has a role in the DNA damage response; at low levels of DNA damage, Sp1 is phosphorylated by ATM and localizes to double-strand break sites where it facilitates DNA double-strand-break repair. Depletion of Sp1 increases the sensitivity of cells to DNA damage, whereas overexpression of Sp1 can drive cells into apoptosis. In response to a variety of stimuli, Sp1 can be regulated through proteolytic cleavage by caspases and/or degradation...
December 13, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29236145/-non-coding-rna-innovative-regulators-with-therapeutic-perspective
#12
A Bührke, C Bär, T Thum
As a result of the Human Genome Project it became evident that only 1-3% of all gene transcripts encode proteins. The vast majority of gene transcripts are in fact characterized as non-coding RNAs (ncRNAs). These ncRNAs have a huge impact on diverse physiological and pathological mechanisms within an organism. In particular, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), which are differentiated by their size and function, are involved in the regulation and development of many illnesses. In the context of heart and cardiovascular diseases numerous ncRNAs have also already been described in some detail...
December 13, 2017: Herz
https://www.readbyqxmd.com/read/29236054/genome-wide-profiling-of-small-rnas-and-degradome-revealed-conserved-regulations-of-mirnas-on-auxin-responsive-genes-during-fruit-enlargement-in-peaches
#13
Mengya Shi, Xiao Hu, Yu Wei, Xu Hou, Xue Yuan, Jun Liu, Yueping Liu
Auxin has long been known as a critical phytohormone that regulates fruit development in plants. However, due to the lack of an enlarged ovary wall in the model plants Arabidopsis and rice, the molecular regulatory mechanisms of fruit division and enlargement remain unclear. In this study, we performed small RNA sequencing and degradome sequencing analyses to systematically explore post-transcriptional regulation in the mesocarp at the hard core stage following treatment of the peach (Prunus persica L.) fruit with the synthetic auxin α-naphthylacetic acid (NAA)...
December 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29235574/ten-principles-of-heterochromatin-formation-and-function
#14
REVIEW
Robin C Allshire, Hiten D Madhani
Heterochromatin is a key architectural feature of eukaryotic chromosomes, which endows particular genomic domains with specific functional properties. The capacity of heterochromatin to restrain the activity of mobile elements, isolate DNA repair in repetitive regions and ensure accurate chromosome segregation is crucial for maintaining genomic stability. Nucleosomes at heterochromatin regions display histone post-translational modifications that contribute to developmental regulation by restricting lineage-specific gene expression...
December 13, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/29235570/targeting-negative-regulation-of-p53-by-mdm2-and-wip1-as-a-therapeutic-strategy-in-cutaneous-melanoma
#15
Chiao-En Wu, Arman Esfandiari, Yi-Hsuan Ho, Nan Wang, Ahmed Khairallah Mahdi, Erhan Aptullahoglu, Penny Lovat, John Lunec
BACKGROUND: Cutaneous melanoma is the most serious skin malignancy and new therapeutic strategies are needed for advanced melanoma. TP53 mutations are rare in cutaneous melanoma and hence activation of wild-type p53 is a potential therapeutic strategy in cutaneous melanoma. Here, we investigated the WIP1 inhibitor, GSK2830371, and MDM2-p53 binding antagonists (nutlin-3, RG7388 and HDM201) alone and in combination treatment in cutaneous melanoma cell lines and explored the mechanistic basis of these responses in relation to the genotype and induced gene expression profile of the cells...
December 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29235495/identification-of-nonsense-mediated-mrna-decay-pathway-as-a-critical-regulator-of-p53-isoform-%C3%AE
#16
Lauren E Cowen, Yi Tang
Human TP53 gene encodes the tumor suppressor p53 and, via alternative splicing, the p53β and γ isoforms. Numerous studies have shown that p53β/γ can modulate p53 functions and are critically involved in regulation of cellular response to stress conditions. However, it is not fully understood how the β and γ isoforms are regulated following splicing. Using gene targeting and RNAi, we showed that depletion of the nonsense-mediated mRNA decay (NMD) factor SMG7 or UPF1 significantly induced p53β but had minimal effect on p53γ...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29235483/a-novel-type-i-cystatin-of-parasite-origin-with-atypical-legumain-binding-domain
#17
Jana Ilgová, Lucie Jedličková, Hana Dvořáková, Michal Benovics, Libor Mikeš, Lubomír Janda, Jiří Vorel, Pavel Roudnický, David Potěšil, Zbyněk Zdráhal, Milan Gelnar, Martin Kašný
Parasite inhibitors of cysteine peptidases are known to influence a vast range of processes linked to a degradation of either the parasites' own proteins or proteins native to their hosts. We characterise a novel type I cystatin (stefin) found in a sanguinivorous fish parasite Eudiplozoon nipponicum (Platyhelminthes: Monogenea). We have identified a transcript of its coding gene in the transcriptome of adult worms. Its amino acid sequence is similar to other stefins except for containing a legumain-binding domain, which is in this type of cystatins rather unusual...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29235474/engineering-cell-signaling-using-tunable-crispr-cpf1-based-transcription-factors
#18
Yuchen Liu, Jinghong Han, Zhicong Chen, Hanwei Wu, Hongsong Dong, Guohui Nie
The catalytically dead Cpf1 endonuclease from Acidaminococcus sp. BV3L6 (dAsCpf1) has been used to construct effective transcriptional repressors in bacteria and plants. However, it is still unclear if dAsCpf1 can function in human cells as a transcriptional regulator or a signal conductor. Here, we repurpose the dAsCpf1 system in human cells for a variety of functions, including the activation or repression of gene transcription. Moreover, we construct programmable ligand-controlled dAsCpf1 systems either by coupling crRNAs with engineered riboswitches or by fusing dAsCpf1 proteins with G protein-coupled receptors...
December 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29235467/in-situ-functional-dissection-of-rna-cis-regulatory-elements-by-multiplex-crispr-cas9-genome-engineering
#19
Qianxin Wu, Quentin R V Ferry, Toni A Baeumler, Yale S Michaels, Dimitrios M Vitsios, Omer Habib, Roland Arnold, Xiaowei Jiang, Stefano Maio, Bruno R Steinkraus, Marta Tapia, Paolo Piazza, Ni Xu, Georg A Holländer, Thomas A Milne, Jin-Soo Kim, Anton J Enright, Andrew R Bassett, Tudor A Fulga
RNA regulatory elements (RREs) are an important yet relatively under-explored facet of gene regulation. Deciphering the prevalence and functional impact of this post-transcriptional control layer requires technologies for disrupting RREs without perturbing cellular homeostasis. Here we describe genome-engineering based evaluation of RNA regulatory element activity (GenERA), a clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 platform for in situ high-content functional analysis of RREs...
December 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29235098/hepcidin-and-dna-promoter-methylation-in-hepatocellular-carcinoma
#20
Silvia Udali, Annalisa Castagna, Michela Corbella, Andrea Ruzzenente, Sara Moruzzi, Filippo Mazzi, Tommaso Campagnaro, Domenica De Santis, Antonia Franceschi, Patrizia Pattini, Rossella Gottardo, Oliviero Olivieri, Luigi Perbellini, Alfredo Guglielmi, Sang-Woon Choi, Domenico Girelli, Simonetta Friso
BACKGROUND: The liver hormone hepcidin regulates iron homeostasis that is often altered in hepatocellular carcinoma (HCC). Epigenetic phenomena control gene expression through a dynamic fashion, therefore, considering the plasticity of both iron homeostasis and epigenetic mechanisms and their role in liver carcinogenesis, we investigated whether hepcidin gene (HAMP) expression is modulated by DNA methylation thus affecting iron status in human HCC. MATERIALS AND METHODS: Thirty-two patients affected by non-viral HCC were enrolled and their main clinical and biochemical characteristics obtained...
December 13, 2017: European Journal of Clinical Investigation
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