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https://www.readbyqxmd.com/read/28548675/inducible-bcl-2-gene-rna-interference-mediated-by-aptamer-integrated-hdv-ribozyme-switch
#1
Yuanyuan Zhang, Jine Wang, Hui Cheng, Na Sun, Min Liu, Zhengyan Wu, Renjun Pei
The regulation of RNA interference (RNAi) could be a powerful method for the study of temporal and dose dependent effects of gene expression. In this study, we designed the hepatitis delta virus (HDV) ribozyme with an embedded theophylline aptamer as the sensor domain and the pri-miRNA of endogenous gene Bcl-2 as the effector domain to engineer an RNAi-regulatory device in MCF-7 cells. The system allowed us to control gene expression by adding theophylline into the culture media in a dose dependent fashion...
May 26, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28546428/the-myocardin-related-transcription-factor-mkl-co-regulates-the-cellular-levels-of-two-profilin-isoforms
#2
Marion Joy, David Gau, Nevin Castellucci, Ron Prywes, Partha Roy
Megakaryoblastic leukemia (MKL)/ serum response factor (SRF)-mediated gene transcription is a highly conserved mechanism that connects dynamic reorganization of the actin cytoskeleton to regulation of expression of a wide range of genes including SRF itself and many important structural and regulatory components of actin cytoskeleton. In this study, we examined the possible role of MKL/SRF in the context of regulation of profilin (Pfn), a major controller of actin dynamics and actin cytoskeletal remodeling in cells...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28541304/digital-logic-circuits-in-yeast-with-crispr-dcas9-nor-gates
#3
Miles W Gander, Justin D Vrana, William E Voje, James M Carothers, Eric Klavins
Natural genetic circuits enable cells to make sophisticated digital decisions. Building equally complex synthetic circuits in eukaryotes remains difficult, however, because commonly used components leak transcriptionally, do not arbitrarily interconnect or do not have digital responses. Here, we designed dCas9-Mxi1-based NOR gates in Saccharomyces cerevisiae that allow arbitrary connectivity and large genetic circuits. Because we used the chromatin remodeller Mxi1, our gates showed minimal leak and digital responses...
May 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28540681/exploring-microrna-target-regulatory-interactions-by-computing-technologies
#4
Yue Hu, Wenjun Lan, Daniel Miller
MiRNA genes (miRNA precursor genes) share some common structural elements with protein genes. As with protein genes, the promoters of miRNA genes are necessary to regulate the expression of miRNA. The computation methods used to find the promoter regions of the protein genes have been applied to miRNA genes and some methods have been designed specifically to find the promoter regions of miRNA genes. The transcription factors (TFs), miRNA, and the targeted genes can form complex regulatory networks in the cells that can be divided into circuits...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28539603/ribosomal-protein-l23-negatively-regulates-cellular-apoptosis-via-the-rpl23-miz-1-c-myc-circuit-in-higher-risk-myelodysplastic-syndrome
#5
Yuekun Qi, Xiao Li, Chunkang Chang, Feng Xu, Qi He, Youshan Zhao, Lingyun Wu
Ribosomal protein (RP) L23 is a negative regulator of cellular apoptosis, and RPL23 overexpression is associated with abnormal apoptotic resistance in CD34+ cells derived from patients with higher-risk myelodysplastic syndrome (MDS). However, the mechanism underlying RPL23-induced apoptotic resistance in higher-risk MDS patients is poorly understood. In this study, we showed that reduced RPL23 expression led to suppressed cellular viability, increased apoptosis and G1-S cell cycle arrest. Gene microarray analysis comparing RPL23-knockdown and control cells identified an array of differentially expressed genes, of which, Miz-1, was upregulated with transactivation of the cell cycle inhibitors p15(Ink4b) and p21(Cip1), and Miz-1's functional repressor, c-Myc, was downregulated...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539478/a-novel-epigenetic-aml1-eto-thap10-mir-383-mini-circuitry-contributes-to-t-8-21-leukaemogenesis
#6
Yonghui Li, Qiaoyang Ning, Jinlong Shi, Yang Chen, Mengmeng Jiang, Li Gao, Wenrong Huang, Yu Jing, Sai Huang, Anqi Liu, Zhirui Hu, Daihong Liu, Lili Wang, Clara Nervi, Yun Dai, Michael Q Zhang, Li Yu
DNA methylation patterns are frequently deregulated in t(8;21) acute myeloid leukaemia (AML), but little is known of the mechanisms by which specific gene sets become aberrantly methylated. Here, we found that the promoter DNA methylation signature of t(8;21)(+) AML blasts differs from that of t(8;21)(-) AMLs. This study demonstrated that a novel hypermethylated zinc finger-containing protein, THAP10, is a target gene and can be epigenetically suppressed by AML1-ETO at the transcriptional level in t(8;21) AML...
May 24, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28538174/schizophrenia-related-microdeletion-impairs-emotional-memory-through-microrna-dependent-disruption-of-thalamic-inputs-to-the-amygdala
#7
Tae-Yeon Eom, Ildar T Bayazitov, Kara Anderson, Jing Yu, Stanislav S Zakharenko
Individuals with 22q11.2 deletion syndrome (22q11DS) are at high risk of developing psychiatric diseases such as schizophrenia. Individuals with 22q11DS and schizophrenia are impaired in emotional memory, anticipating, recalling, and assigning a correct context to emotions. The neuronal circuits responsible for these emotional memory deficits are unknown. Here, we show that 22q11DS mouse models have disrupted synaptic transmission at thalamic inputs to the lateral amygdala (thalamo-LA projections). This synaptic deficit is caused by haploinsufficiency of the 22q11DS gene Dgcr8, which is involved in microRNA processing, and is mediated by the increased dopamine receptor Drd2 levels in the thalamus and by reduced probability of glutamate release from thalamic inputs...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28536069/crispr-engineered-genome-editing-for-the-next-generation-neurological-disease-modeling
#8
REVIEW
Weijun Feng, Hai-Kun Liu, Daisuke Kawauchi
Neurological disorders often occur because of failure of proper brain development and/or appropriate maintenance of neuronal circuits. In order to understand roles of causative factors (e.g. genes, cell types) in disease development, generation of solid animal models has been one of straight-forward approaches. Recent next generation sequencing studies on human patient-derived clinical samples have identified various types of recurrent mutations in individual neurological diseases. While these discoveries have prompted us to evaluate contribution of mutated genes to these neurological diseases, a feasible but flexible genome editing tool had remained to be developed...
May 20, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28533765/leptin-induces-mitosis-and-activates-the-canonical-wnt-%C3%AE-catenin-signaling-pathway-in-neurogenic-regions-of-xenopus-tadpole-brain
#9
Melissa Cui Bender, Christopher J Sifuentes, Robert J Denver
In addition to its well-known role as an adipostat in adult mammals, leptin has diverse physiological and developmental actions in vertebrates. Leptin has been shown to promote development of hypothalamic circuits and to induce mitosis in different brain areas of mammals. We investigated the ontogeny of leptin mRNA, leptin actions on cell proliferation in the brain, and gene expression in the preoptic area/hypothalamus of tadpoles of Xenopus laevis. The level of leptin mRNA was low in premetamorphic tadpoles, but increased strongly at the beginning of metamorphosis and peaked at metamorphic climax...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28532217/integration-of-bacterial-small-rnas-in-regulatory-networks
#10
Mor Nitzan, Rotem Rehani, Hanah Margalit
Small RNAs (sRNAs) are central regulators of gene expression in bacteria, controlling target genes posttranscriptionally by base pairing with their mRNAs. sRNAs are involved in many cellular processes and have unique regulatory characteristics. In this review, we discuss the properties of regulation by sRNAs and how it differs from and combines with transcriptional regulation. We describe the global characteristics of the sRNA-target networks in bacteria using graph-theoretic approaches and review the local integration of sRNAs in mixed regulatory circuits, including feed-forward loops and their combinations, feedback loops, and circuits made of an sRNA and another regulator, both derived from the same transcript...
May 22, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28532215/matrix-mechanosensing-from-scaling-concepts-in-omics-data-to-mechanisms-in-the-nucleus-regeneration-and-cancer
#11
Dennis E Discher, Lucas Smith, Sangkyun Cho, Mark Colasurdo, Andrés J García, Sam Safran
Many of the most important molecules of life are polymers. In animals, the most abundant of the proteinaceous polymers are the collagens, which constitute the fibrous matrix outside cells and which can also self-assemble into gels. The physically measurable stiffness of gels, as well as tissues, increases with the amount of collagen, and cells seem to sense this stiffness. An understanding of this mechanosensing process in complex tissues, including fibrotic disease states with high collagen, is now utilizing 'omics data sets and is revealing polymer physics-type, nonlinear scaling relationships between concentrations of seemingly unrelated biopolymers...
May 22, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28532145/mini-photobioreactors-for-in-vivo-real-time-characterization-and-evolutionary-tuning-of-bacterial-optogenetic-circuit
#12
Hsinkai Wang, Ya-Tang Yang
The current standard protocols for characterizing the optogenetic circuit of bacterial cells using flow cytometry in light tubes and light exposure of culture plates are tedious, labor-intensive, and cumbersome. In this work, we engineer a bioreactor with working volume of ~10 mL for in vivo real-time optogenetic characterization of E. coli with a CcaS-CcaR light-sensing system. In the bioreactor, optical density measurements, reporter protein fluorescence detection, and light input stimuli are provided by four light-emitting diode sources and two photodetectors...
May 22, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28526829/super-enhancers-and-broad-h3k4me3-domains-form-complex-gene-regulatory-circuits-involving-chromatin-interactions
#13
Fan Cao, Yiwen Fang, Hong Kee Tan, Yufen Goh, Jocelyn Yeen Hui Choy, Bryan Thean Howe Koh, Jiong Hao Tan, Nicolas Bertin, Aroul Ramadass, Ewan Hunter, Jayne Green, Matthew Salter, Alexandre Akoulitchev, Wilson Wang, Wee Joo Chng, Daniel G Tenen, Melissa J Fullwood
Stretched histone regions, such as super-enhancers and broad H3K4me3 domains, are associated with maintenance of cell identity and cancer. We connected super-enhancers and broad H3K4me3 domains in the K562 chronic myelogenous leukemia cell line as well as the MCF-7 breast cancer cell line with chromatin interactions. Super-enhancers and broad H3K4me3 domains showed higher association with chromatin interactions than their typical counterparts. Interestingly, we identified a subset of super-enhancers that overlap with broad H3K4me3 domains and show high association with cancer-associated genes including tumor suppressor genes...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28525642/dynamics-of-sequestration-based-gene-regulatory-cascades
#14
Tatenda Shopera, William R Henson, Tae Seok Moon
Gene regulatory cascades are ubiquitous in biology. Because regulatory cascades are integrated within complex networks, their quantitative analysis is challenging in native systems. Synthetic biologists have gained quantitative insights into the properties of regulatory cascades by building simple circuits, but sequestration-based regulatory cascades remain relatively unexplored. Particularly, it remains unclear how the cascade components collectively control the output dynamics. Here, we report the construction and quantitative analysis of the longest sequestration-based cascade in Escherichia coli...
May 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28524655/tunable-control-of-an-escherichia-coli-expression-system-for-the-overproduction-of-membrane-proteins-by-titrated-expression-of-a-mutant-lac-repressor
#15
Seong Keun Kim, Dae-Hee Lee, Oh Cheol Kim, Jihyun F Kim, Sung Ho Yoon
Most inducible expression systems suffer from growth defects, leaky basal induction, and inhomogeneous expression levels within a host cell population. These difficulties are most prominent with the overproduction of membrane proteins that are toxic to host cells. Here, we developed an Escherichia coli inducible expression system for membrane protein production based on titrated expression of a mutant lac repressor (mLacI). Performance of the mLacI inducible system was evaluated in conjunction with commonly used lac operator-based expression vectors using a T7 or tac promoter...
May 19, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28524267/synaptic-activity-suppresses-expression-of-neurogenic-differentiation-factor-2-in-an-nmda-receptor-dependent-manner
#16
Fading Chen, Benjamin J Hall
Neurogenic differentiation factor 2 (NeuroD2) is a highly expressed transcription factor in the developing central nervous system. In newborn neurons, NeuroD2-mediated gene expression promotes differentiation, maturation, and survival. In addition to these early, cell-intrinsic developmental processes, NeuroD2 in post-mitotic neurons also regulates synapse growth and ion channel expression to control excitability. While NeuroD2 transactivation can be induced in an activity-dependent manner, little is known about how expression of NeuroD2 itself is regulated...
May 19, 2017: Synapse
https://www.readbyqxmd.com/read/28516429/cardinal-epigenetic-role-of-non-coding-regulatory-rnas-in-circadian-rhythm
#17
REVIEW
Utpal Bhadra, Pradipta Patra, Manika Pal-Bhadra
Circadian rhythm which governs basic physiological activities like sleeping, feeding and energy consumption is regulated by light-controlled central clock genes in the pacemaker neuron. The timekeeping machinery with unique transcriptional and post-transcriptional feedback loops is controlled by different small regulatory RNAs in the brain. Roles of the multiple neuronal genes, especially post-transcriptional regulation, splicing, polyadenylation, mature mRNA editing, and stability of translation products, are controlled by epigenetic activities orchestrated via small RNAs...
May 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28514446/identification-of-preoptic-sleep-neurons-using-retrograde-labelling-and-gene-profiling
#18
Shinjae Chung, Franz Weber, Peng Zhong, Chan Lek Tan, Thuc Nghi Nguyen, Kevin T Beier, Nikolai Hörmann, Wei-Cheng Chang, Zhe Zhang, Johnny Phong Do, Shenqin Yao, Michael J Krashes, Bosiljka Tasic, Ali Cetin, Hongkui Zeng, Zachary A Knight, Liqun Luo, Yang Dan
In humans and other mammalian species, lesions in the preoptic area of the hypothalamus cause profound sleep impairment, indicating a crucial role of the preoptic area in sleep generation. However, the underlying circuit mechanism remains poorly understood. Electrophysiological recordings and c-Fos immunohistochemistry have shown the existence of sleep-active neurons in the preoptic area, especially in the ventrolateral preoptic area and median preoptic nucleus. Pharmacogenetic activation of c-Fos-labelled sleep-active neurons has been shown to induce sleep...
May 17, 2017: Nature
https://www.readbyqxmd.com/read/28511982/characteristic-and-intermingled-neocortical-circuits-encode-different-visual-object-discriminations
#19
Guo-Rong Zhang, Hua Zhao, Nathan Cook, Michael Svestka, Eui M Choi, Mary Jan, Robert G Cook, Alfred I Geller
Synaptic plasticity and neural network theories hypothesize that the essential information for advanced cognitive tasks is encoded in specific circuits and neurons within distributed neocortical networks. However, these circuits are incompletely characterized, and we do not know if a specific discrimination is encoded in characteristic circuits among multiple animals. Here, we determined the spatial distribution of active neurons for a circuit that encodes some of the essential information for a cognitive task...
May 13, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28510022/aspects-of-protein-dna-interactions-a-review-of-quantitative-thermodynamic-theory-for-modelling-synthetic-circuits-utilising-laci-and-ci-repressors-iptg-and-the-reporter-gene-lacz
#20
REVIEW
Peter D Munro, Gary K Ackers, Keith E Shearwin
Protein-DNA interactions are central to the control of gene expression across all forms of life. The development of approaches to rigorously model such interactions has often been hindered both by a lack of quantitative binding data and by the difficulty in accounting for parameters relevant to the intracellular situation, such as DNA looping and thermodynamic non-ideality. Here, we review these considerations by developing a thermodynamically based mathematical model that attempts to simulate the functioning of an Escherichia coli expression system incorporating two of the best characterised prokaryotic DNA binding proteins, Lac repressor and lambda CI repressor...
December 2016: Biophysical Reviews
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