scholarly journals Functional insights into the role of nuclear-retained long noncoding RNAs in gene expression control in mammalian cells

2013 ◽  
Vol 21 (6-7) ◽  
pp. 695-711 ◽  
Author(s):  
Deepak K. Singh ◽  
Kannanganattu V. Prasanth
Keyword(s):  
Gene Expression ◽  
Mammalian Cells ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Expression Control ◽  
Gene Expression Control

scholarly journals High-performance chemical- and light-inducible recombinases in mammalian cells and mice

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Benjamin H. Weinberg ◽  
Jang Hwan Cho ◽  
Yash Agarwal ◽  
N. T. Hang Pham ◽  
Leidy D. Caraballo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mammalian Cells ◽  
High Performance ◽  
Genome Engineering ◽  
Genetic Circuits ◽  
Control Of Gene Expression ◽  
Expression Control ◽  
Gene Expression Control ◽  
High Performance Systems ◽  
Spatiotemporal Control

Abstract Site-specific DNA recombinases are important genome engineering tools. Chemical- and light-inducible recombinases, in particular, enable spatiotemporal control of gene expression. However, inducible recombinases are scarce due to the challenge of engineering high performance systems, thus constraining the sophistication of genetic circuits and animal models that can be created. Here we present a library of >20 orthogonal inducible split recombinases that can be activated by small molecules, light and temperature in mammalian cells and mice. Furthermore, we engineer inducible split Cre systems with better performance than existing systems. Using our orthogonal inducible recombinases, we create a genetic switchboard that can independently regulate the expression of 3 different cytokines in the same cell, a tripartite inducible Flp, and a 4-input AND gate. We quantitatively characterize the inducible recombinases for benchmarking their performances, including computation of distinguishability of outputs. This library expands capabilities for multiplexed mammalian gene expression control.

scholarly journals Long Noncoding RNA Plays a Key Role in Metastasis and Prognosis of Hepatocellular Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Guangbing Li ◽  
Haohai Zhang ◽  
Xueshuai Wan ◽  
Xiaobo Yang ◽  
Chengpei Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Regulation Of Gene Expression ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Comprehensive Review ◽  
Cellular Processes

Long noncoding RNAs (lncRNAs) have been attracting immense research interests. However, only a handful of lncRNAs had been thoroughly characterized. They were involved in fundamental cellular processes including regulation of gene expression at epigenetics as well as tumorogenesis. In this paper, we give a systematic and comprehensive review of existing literature about lncRNA involvement in hepatocellular carcinoma. This review exhibited that lncRNAs played important roles in tumorigenesis and subsequent prognosis and metastasis of hepatocellular carcinoma and elucidated the role of some specific lncRNAs such as MALAT1 and HOTAIR in the pathophysiology of hepatocellular carcinoma and their potential of being therapeutic targets.

Abstract 456: High Fat Diet-Induced Atherosclerosis-Driven Myocardial Infarction: Role of Cardiac Long Noncoding RNAs in Triiodo-L-Thyronine-Mediated Protection

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Viswanathan Rajagopalan ◽  
Emily Schultz ◽  
Youhua Zhang ◽  
Olga Savinova ◽  
Clifford Costello ◽  
...  
Keyword(s):  
Gene Expression ◽  
Myocardial Infarction ◽  
Median Survival ◽  
Refractory Period ◽  
Noncoding Rnas ◽  
Left Ventricular ◽  
Long Noncoding Rnas ◽  
Gradual Transition ◽  
High Fat

Novel mechanisms associated with therapeutically safe thyroid hormone (TH) therapy are emerging. We have shown that oral triiodo-L-thyronine (T3) offers safe cardioprotection in coronary ligation myocardial infarction (MI), ligation ischemia-reperfusion injury, diabetic cardiomyopathy, etc. via restoration of gene expression. However, safe therapeutic effects following atherosclerosis-driven MI and role of long noncoding RNAs (lncRNAs) is unknown. We employed a mouse model of scavenger receptor B1 knockout with hypomorphic apolipoprotein E. Young adult heterozygote littermates served as controls and all mice received high fat (HF) diet for one month. Along with HF diet, a cohort of homozygotes (HypoE) received therapeutic dose of T3 (5.5 μg/kg/d) in drinking water ad libitum. In HypoE mice, Paigen HF diet induced interstitial fibrotic MI with severe hypertrophic (Heart wt./Body wt., HW/BW: control:4.6±0.14; HypoE:12.9±0.75; p<0.0001) heart failure, depressed left ventricular (LV) contractility, increased end-diastolic pressure, myocyte disarray/loss, vacuolization and inflammatory cell infiltration. Aortic root showed atheromatous lipid deposits and median survival time was 26 days. Cholate-free paigen HF diet, used to achieve more gradual transition showed moderate hypertrophy (HW/BW: control:4.9±0.1; HypoE:7.9±0.95; ; p<0.01), decreased LV contractility, increasing atrial effective refractory period with a median survival of 41.5 days. Other changes include decreased serum thyroxine, increased serum cholesterol, significant splenomegaly and alterations in real-time gene expression of numerous cardiac lncRNAs and limited serum lncRNAs involved in inflammatory and immune responses (>2-fold; p<0.05). Oral T3 therapy with cholate-free diet partially restored LV contractility, atrial refractory period and cardiac lncRNAs without significantly affecting serum lncRNAs. These were accompanied by expected feedback inhibition of thyroxine without negatively impacting hypertrophy or heart rate. This is the first study to show a novel role of lncRNAs in TH-mediated cardioprotection. It also demonstrates possibility of safe preventive T3 therapy in a clinically relevant early coronary artery disease model.

The Role of the Epigenome in Gene Expression Control and the Epimark Changes in Response to the Environment

2014 ◽  
Vol 33 (1) ◽  
pp. 64-87 ◽  
Author(s):  
Michael J. Van Oosten ◽  
Ray A. Bressan ◽  
Jian-Kang Zhu ◽  
Hans J. Bohnert ◽  
Viswanathan Chinnusamy
Keyword(s):  
Gene Expression ◽  
Expression Control ◽  
Gene Expression Control

scholarly journals Noise-reducing optogenetic negative-feedback gene circuits in human cells

2019 ◽  
Vol 47 (14) ◽  
pp. 7703-7714 ◽  
Author(s):  
Michael Tyler Guinn ◽  
Gábor Balázsi
Keyword(s):  
Gene Expression ◽  
Noise Reduction ◽  
Negative Feedback ◽  
Mammalian Cells ◽  
Cellular Proliferation ◽  
Protein Domain ◽  
Gene Circuits ◽  
Expression Control ◽  
Gene Expression Control

Abstract Gene autorepression is widely present in nature and is also employed in synthetic biology, partly to reduce gene expression noise in cells. Optogenetic systems have recently been developed for controlling gene expression levels in mammalian cells, but most have utilized activator-based proteins, neglecting negative feedback except for in silico control. Here, we engineer optogenetic gene circuits into mammalian cells to achieve noise-reduction for precise gene expression control by genetic, in vitro negative feedback. We build a toolset of these noise-reducing Light-Inducible Tuner (LITer) gene circuits using the TetR repressor fused with a Tet-inhibiting peptide (TIP) or a degradation tag through the light-sensitive LOV2 protein domain. These LITers provide a range of nearly 4-fold gene expression control and up to 5-fold noise reduction from existing optogenetic systems. Moreover, we use the LITer gene circuit architecture to control gene expression of the cancer oncogene KRAS(G12V) and study its downstream effects through phospho-ERK levels and cellular proliferation. Overall, these novel LITer optogenetic platforms should enable precise spatiotemporal perturbations for studying multicellular phenotypes in developmental biology, oncology and other biomedical fields of research.

The Role of Long Noncoding RNAs in the Epigenetic Control of Gene Expression

ChemMedChem ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. 505-510 ◽  
Author(s):  
Mariangela Morlando ◽  
Monica Ballarino ◽  
Alessandro Fatica ◽  
Irene Bozzoni
Keyword(s):  
Gene Expression ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Control Of Gene Expression ◽  
Epigenetic Control

scholarly journals Noise-Reducing Negative-Feedback Optogenetic Circuits in Mammalian Cells

2019 ◽  
Author(s):  
Michael Tyler Guinn ◽  
Gábor Balázsi
Keyword(s):  
Gene Expression ◽  
Noise Reduction ◽  
Negative Feedback ◽  
Mammalian Cells ◽  
Cellular Proliferation ◽  
Protein Domain ◽  
Inhibitory Peptide ◽  
Gene Circuits ◽  
Expression Control ◽  
Gene Expression Control

AbstractGene autorepression is widely present in nature and is also employed in synthetic biology, partly to reduce gene expression noise in cells. Optogenetic systems have recently been employed for controlling gene expression levels in mammalian cells, but most have utilized activator-based proteins, neglecting negative feedback. Here, we engineer optogenetic negative-feedback gene circuits in mammalian cells to achieve noise-reduction for precise gene expression control. We build a toolset of these noise-reducing Light-Inducible Tuner (LITer) gene circuits using the TetR repressor fused with a Tet-Inhibitory peptide (TIP) or a degradation tag through the light-sensitive LOV2 protein domain. These LITers provide nearly a range of 4-fold gene expression control and up to five-fold noise reduction from existing optogenetic systems. Moreover, we use the LITer gene circuit architecture to control gene expression of the cancer oncogene KRAS(G12V) and study its downstream effects through phospho-ERK levels and cellular proliferation. Overall, these novel LITer optogenetic platforms should enable precise spatiotemporal perturbations for studying multicellular phenotypes in developmental biology, oncology, and other biomedical fields of research.

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