scholarly journals Bi-directional gene switching with the tetracycline repressor and a novel tetracycline antagonist

1996 ◽  
Vol 24 (15) ◽  
pp. 2900-2904 ◽  
Author(s):  
J Chrast-Balz
Keyword(s):  
Gene Switching ◽  
Tetracycline Repressor

scholarly journals Integrating genome sequence and structural data for statistical learning to predict transcription factor binding sites

2020 ◽  
Vol 48 (22) ◽  
pp. 12604-12617
Author(s):  
Pengpeng Long ◽  
Lu Zhang ◽  
Bin Huang ◽  
Quan Chen ◽  
Haiyan Liu
Keyword(s):  
Genome Sequence ◽  
Energy Function ◽  
Structural Information ◽  
Structural Data ◽  
P Values ◽  
A Genome ◽  
Z Scores ◽  
Transcription Regulators ◽  
Dna Specificity ◽  
Tetracycline Repressor

Abstract We report an approach to predict DNA specificity of the tetracycline repressor (TetR) family transcription regulators (TFRs). First, a genome sequence-based method was streamlined with quantitative P-values defined to filter out reliable predictions. Then, a framework was introduced to incorporate structural data and to train a statistical energy function to score the pairing between TFR and TFR binding site (TFBS) based on sequences. The predictions benchmarked against experiments, TFBSs for 29 out of 30 TFRs were correctly predicted by either the genome sequence-based or the statistical energy-based method. Using P-values or Z-scores as indicators, we estimate that 59.6% of TFRs are covered with relatively reliable predictions by at least one of the two methods, while only 28.7% are covered by the genome sequence-based method alone. Our approach predicts a large number of new TFBs which cannot be correctly retrieved from public databases such as FootprintDB. High-throughput experimental assays suggest that the statistical energy can model the TFBSs of a significant number of TFRs reliably. Thus the energy function may be applied to explore for new TFBSs in respective genomes. It is possible to extend our approach to other transcriptional factor families with sufficient structural information.

scholarly journals Serum factors can modulate the developmental clock of gamma- to beta-globin gene switching in somatic cell hybrids.

1993 ◽  
Vol 13 (8) ◽  
pp. 4844-4851 ◽  
Author(s):  
G Zitnik ◽  
Q Li ◽  
G Stamatoyannopoulos ◽  
T Papayannopoulou
Keyword(s):  
Globin Gene ◽  
Cumulative Number ◽  
Beta Globin ◽  
Serum Factors ◽  
Beta Globin Gene ◽  
Cell Divisions ◽  
Growth Promoting ◽  
Gene Switching ◽  
Mouse Erythroleukemia

The fusion of human fetal erythroid (HFE) cells with mouse erythroleukemia (MEL) cells produces stable synkaryons (HFE x MEL) which can be monitored for extended periods of time in culture. Initially these hybrids express a human fetal globin program (gamma >> beta), but after weeks or months in culture, they switch to an adult pattern of globin expression (beta >> gamma). The rate at which hybrids switch to the adult phenotype is roughly dependent on the gestational age of the fetal erythroid cells used in the fusion, suggesting that the rate of switching in vitro may be determined by a developmental clock type of mechanism, possibly involving the cumulative number of divisions experienced by the human fetal cells. To investigate whether the number or rate of cell divisions postfusion can influence the rate of switching, we monitored the rate of switching in hybrids from independent fusions under growth-promoting (serum-replete) and growth-suppressing (serum-deprived) conditions. We found that hybrids grown under serum-deprived or serumless conditions switched more rapidly to adult globin expression than did their counterparts in serum-replete conditions. Neither the number of cumulative cell divisions nor time in culture per se predicted the rate of switching in vitro. Our data suggest that factors present in serum either retard switching of hybrids by their presence or promote switching by their absence, indicating that globin switching in vitro can be modulated by the environment; however, once switching in HFE x MEL hybrids is complete, serum factors cannot reverse this process.

Feedback-Induced Variations of Distribution in a Representative Gene Model

2015 ◽  
Vol 25 (07) ◽  
pp. 1540008
Author(s):  
Peijiang Liu ◽  
Zhanjiang Yuan ◽  
Lifang Huang ◽  
Tianshou Zhou
Keyword(s):  
Gene Expression ◽  
Power Law ◽  
Positive Feedback ◽  
Bimodal Distribution ◽  
Stochastic Bifurcation ◽  
Protein Distribution ◽  
Identical Cell ◽  
Induced Changes ◽  
Gene Switching ◽  
Cell To Cell Variability

Gene expression is inherently noisy, implying that the number of mRNAs or proteins is not invariant rather than follows a distribution. This distribution can not only provide the exact information on the dynamics of gene expression but also describe cell-to-cell variability in a genetically identical cell population. Here, we systematically investigate a two-state model of gene expression, a model paradigm used to study expression dynamics, focusing on the effect of feedback on the type of mRNA or protein distribution. If there is no feedback, then the distribution may be bimodal, power-law tailed, or Poisson-like, depending on gene switching rates. However, we find that feedback can tune or change the type of the distribution in each case and tends to unimodalize the distribution as its strength increases. Specifically, positive feedback can change not only a power-law tailed distribution into a bimodal or Poisson-like distribution but also a bimodal distribution into a Poisson-like distribution (implying that stochastic bifurcation can take place). In addition, it can make a Poisson-like distribution become more peaked but does not change the type of this distribution. In contrast to positive feedback, negative feedback has less influence on the shape of the distributions except for the bimodal case. In all cases, the noise-feedback curve used extensively in previous studies cannot well reflect the feedback-induced changes in the shape of distributions. Feedback-induced variations in distribution would be important for cell survival in fluctuating environments.

Developmental regulation of β-globin gene switching

Cell ◽  
1988 ◽  
Vol 55 (1) ◽  
pp. 17-26 ◽  
Author(s):  
Ok-Ryun Baik Choi ◽  
James Douglas Engel
Keyword(s):  
Developmental Regulation ◽  
Globin Gene ◽  
Gene Switching

scholarly journals Modular organisation of inducer recognition and allostery in the tetracycline repressor

FEBS Journal ◽  
2016 ◽  
Vol 283 (11) ◽  
pp. 2102-2114 ◽  
Author(s):  
Sebastiaan Werten ◽  
Julia Schneider ◽  
Gottfried Julius Palm ◽  
Winfried Hinrichs
Keyword(s):  
Modular Organisation ◽  
Tetracycline Repressor

scholarly journals Intravenous Delivery of piggyBac Transposons as a Useful Tool for Liver-Specific Gene-Switching

2018 ◽  
Vol 19 (11) ◽  
pp. 3452 ◽  
Author(s):  
Shingo Nakamura ◽  
Masayuki Ishihara ◽  
Satoshi Watanabe ◽  
Naoko Ando ◽  
Masato Ohtsuka ◽  
...  
Keyword(s):  
Plasmid Dna ◽  
Chain Gene ◽  
Specific Gene ◽  
Chromosomal Integration ◽  
Hepatic Disorder ◽  
Murine Liver ◽  
A Chain ◽  
Gene Switching

Hydrodynamics-based gene delivery (HGD) is an efficient method for transfecting plasmid DNA into hepatocytes in vivo. However, the resulting gene expression is transient, and occurs in a non-tissue specific manner. The piggyBac (PB) transposon system allows chromosomal integration of a transgene in vitro. This study aimed to achieve long-term in vivo expression of a transgene by performing hepatocyte-specific chromosomal integration of the transgene using PB and HGD. Using this approach, we generated a novel mouse model for a hepatic disorder. A distinct signal from the reporter plasmid DNA was discernible in the murine liver approximately two months after the administration of PB transposons carrying a reporter gene. Then, to induce the hepatic disorder, we first administered mice with a PB transposon carrying a CETD unit (loxP-flanked stop cassette, diphtheria toxin-A chain gene, and poly(A) sites), and then with a plasmid expressing the Cre recombinase under the control of a liver-specific promoter. We showed that this system can be used for in situ manipulation and analysis of hepatocyte function in vivo in non-transgenic (Tg) animals.

scholarly journals Analysis of stochastic timing of intracellular events with gene switching

2019 ◽  
Author(s):  
Khem Raj Ghusinga ◽  
Abhyudai Singh
Keyword(s):  
First Passage Time ◽  
Regulatory Protein ◽  
Gene Activation ◽  
Threshold Level ◽  
Passage Time ◽  
First Passage ◽  
Cellular Processes ◽  
Event Timing ◽  
Activation Rates ◽  
Gene Switching

AbstractAn important step in execution of several cellular processes is accumulation of a regulatory protein up to a specific threshold level. Since production of a protein is inherently stochastic, the time at which its level crosses a threshold exhibits cell-to-cell variation. A problem of interest is to characterize how the statistics of event timing is affected by various steps of protein expression. Our previous work studied this problem by considering a gene expression model where gene was always active. Here we extend our analysis to a scenario where gene stochastically switches between active and inactive states. We formulate event timing as the first-passage time for a protein’s level to cross a threshold and investigate how the rates of gene activation/inactivation affect the distribution and moments of the first-passage time. Our results show that both the time-scale of gene switching with respect to the protein degradation rate as well as the ratio of the gene inactivation to gene activation rates are important parameters in shaping the event-timing distribution.

Sign in / Sign up

Export Citation Format

Share Document