scholarly journals Transcriptional Regulation Factors of the Human Mitochondrial Aspartate/Glutamate Carrier Gene, Isoform 2 (SLC25A13): USF1 as Basal Factor and FOXA2 as Activator in Liver Cells

2019 ◽  
Vol 20 (8) ◽  
pp. 1888 ◽  
Author(s):  
Paolo Convertini ◽  
Simona Todisco ◽  
Francesco De Santis ◽  
Ilaria Pappalardo ◽  
Dominga Iacobazzi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Proximal Promoter ◽  
Inner Mitochondrial Membrane ◽  
Gene Encoding ◽  
Putative Promoter Region ◽  
Cell Functions ◽  
Hepatic Cells ◽  
Wide Range ◽  
Aspartate Glutamate Carrier

Mitochondrial carriers catalyse the translocation of numerous metabolites across the inner mitochondrial membrane, playing a key role in different cell functions. For this reason, mitochondrial carrier gene expression needs tight regulation. The human SLC25A13 gene, encoding for the mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), catalyses the electrogenic exchange of aspartate for glutamate plus a proton, thus taking part in many metabolic processes including the malate-aspartate shuttle. By the luciferase (LUC) activity of promoter deletion constructs we identified the putative promoter region, comprising the proximal promoter (−442 bp/−19 bp), as well as an enhancer region (−968 bp/−768 bp). Furthermore, with different approaches, such as in silico promoter analysis, gene silencing and chromatin immunoprecipitation, we identified two transcription factors responsible for SLC25A13 transcriptional regulation: FOXA2 and USF1. USF1 acts as a positive transcription factor which binds to the basal promoter thus ensuring SLC25A13 gene expression in a wide range of tissues. The role of FOXA2 is different, working as an activator in hepatic cells. As a tumour suppressor, FOXA2 could be responsible for SLC25A13 high expression levels in liver and its downregulation in hepatocellular carcinoma (HCC).

scholarly journals Decoding transcriptional regulation via a human gene expression predictor

2020 ◽  
Author(s):  
Yuzhou Wang ◽  
Yu Zhang ◽  
Jiazhen Gong ◽  
Jianqiang Bao ◽  
Shisong Ma
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Stress Response ◽  
Target Gene ◽  
Target Genes ◽  
Human Gene ◽  
Human Gene Expression ◽  
Novel Approach ◽  
Wide Range

ABSTRACTTranscription factors (TF) regulate cellular activities via controlling gene expression, but a predictive model describing how TFs quantitatively modulate human transcriptomes was lacking. We constructed a universal human gene expression predictor and utilized it to decode transcriptional regulation. Using 1613 TFs’ expression, the predictor reconstituted highly accurate transcriptomes for samples derived from a wide range of tissues and conditions. The predictor’s broad applicability indicated it had recapitulated the quantitative relationships between TFs and target genes ubiquitous across tissues. Significant interacting TF-target gene pairs were then extracted from the predictor and enabled downstream inference of TF regulators for diverse pathways involved in development, immunity, metabolism, and stress response. Thus, we present a novel approach to study human transcriptional regulation following the “understanding by modeling” principle.

Transcriptional regulation of human UGT1A1 gene expression through distal and proximal promoter motifs: implication of defects in the UGT1A1 gene promoter

2008 ◽  
Vol 377 (4-6) ◽  
pp. 597-605 ◽  
Author(s):  
Junko Sugatani ◽  
Kousuke Mizushima ◽  
Makoto Osabe ◽  
Kasumi Yamakawa ◽  
Satoru Kakizaki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Gene Promoter ◽  
Proximal Promoter ◽  
Ugt1a1 Gene

scholarly journals Stochastic steady state gain in a gene expression process with mRNA degradation control

2012 ◽  
Vol 9 (72) ◽  
pp. 1589-1598 ◽  
Author(s):  
Hiroyuki Kuwahara ◽  
Russell Schwartz
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Steady State ◽  
Protein Level ◽  
Mrna Level ◽  
System Level ◽  
Wide Range ◽  
Molecular Reactions ◽  
Transcriptional Bursting ◽  
Regulation Model

Recent analyses with high-resolution single-molecule experimental methods have shown highly irregular and variable bursting of mRNA in a wide range of organisms. Noise in gene expression is thought to be beneficial in cell fate specifications, as it can lay a foundation for phenotypic diversification of isogenetic cells in the homogeneous environment. However, because the stability of proteins is, in many cases, higher than that of mRNAs, noise from transcriptional bursting can be considerably buffered at the protein level, limiting the effect of noisy mRNAs at a more global regulation level. This raises a question as to what constructive role noisy mRNAs can play in the system-level dynamics. In this study, we have addressed this question using the computational models that extend the conventional transcriptional bursting model with a post-transcriptional regulation step. Surprisingly, by comparing this stochastic model with the corresponding deterministic model, we find that intrinsic fluctuations can substantially increase the expected mRNA level. Because effects of a higher mRNA level can be transmitted to the protein level even with slow protein degradation rates, this finding suggests that an increase in the protein level is another potential effect of transcriptional bursting. Here, we show that this striking steady state increase is caused by the asynchronous nature of molecular reactions, which allows the transcriptional regulation model to create additional modes of qualitatively distinct dynamics. Our results illustrate non-intuitive effects of reaction asynchronicity on system dynamics that cannot be captured by the traditional deterministic framework. Because molecular reactions are intrinsically stochastic and asynchronous, these findings may have broad implications in modelling and understanding complex biological systems.

scholarly journals Distal and proximal hypoxia response elements cooperate to regulate organ-specific erythropoietin gene expression

Haematologica ◽  
2019 ◽  
Vol 105 (12) ◽  
pp. 2774-2784 ◽  
Author(s):  
Ilaria M.C. Orlando ◽  
Véronique N. Lafleur ◽  
Federica Storti ◽  
Patrick Spielmann ◽  
Lisa Crowther ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Neuronal Cells ◽  
Hypoxia Inducible Factor ◽  
Proximal Promoter ◽  
Hypoxia Response ◽  
Response Elements ◽  
Hepatic Cells ◽  
Specific Manner ◽  
Organ Specific

While it is well-established that distal hypoxia response elements (HREs) regulate hypoxia-inducible factor (HIF) target genes such as erythropoietin (Epo), an interplay between multiple distal and proximal (promoter) HREs has not been described so far. Hepatic Epo expression is regulated by a HRE located downstream of the EPO gene, but this 3' HRE is dispensable for renal EPO gene expression. We previously identified a 5' HRE and could show that both HREs direct exogenous reporter gene expression. Here, we show that whereas in hepatic cells the 3' but not the 5' HRE is required, in neuronal cells both the 5' and 3' HREs contribute to endogenous Epo induction. Moreover, two novel putative HREs were identified in the EPO promoter. In hepatoma cells HIF interacted mainly with the distal 3' HRE, but in neuronal cells HIF most strongly bound the promoter, to a lesser extent the 3' HRE, and not at all the 5' HRE. Interestingly, mutation of either of the two distal HREs abrogated HIF binding to the 3' and promoter HREs. These results suggest that a canonical functional HRE can recruit multiple, not necessarily HIF, transcription factors to mediate HIF binding to different distant HREs in an organ-specific manner.

Interplay between Pur α and Egr-1 in the transcriptional regulation of amyloid precursor protein gene expression

2010 ◽  
Vol 34 (8) ◽  
pp. S27-S27
Author(s):  
Jianqi Cui ◽  
Xiuying Pei ◽  
Qian Zhang ◽  
Bassel E. Sawaya ◽  
Xiaohong Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Amyloid Precursor Protein ◽  
Protein Gene ◽  
Precursor Protein ◽  
Amyloid Precursor Protein Gene

Reverse Screening Bioinformatics Approach to Identify Potential Anti Breast Cancer Targets Using Thymoquinone from Neutraceuticals Black Cumin Oil

2019 ◽  
Vol 19 (5) ◽  
pp. 599-609 ◽  
Author(s):  
Sumathi Sundaravadivelu ◽  
Sonia K. Raj ◽  
Banupriya S. Kumar ◽  
Poornima Arumugamand ◽  
Padma P. Ragunathan
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Cycle ◽  
Cell Death ◽  
In Silico ◽  
Chemotherapeutic Agents ◽  
Normal Cells ◽  
Black Cumin ◽  
In Silico Docking ◽  
Wide Range

Background: Functional foods, neutraceuticals and natural antioxidants have established their potential roles in the protection of human health and diseases. Thymoquinone (TQ), the main bioactive component of Nigella sativa seeds (black cumin seeds), a plant derived neutraceutical was used by ancient Egyptians because of their ability to cure a variety of health conditions and used as a dietary food supplement. Owing to its multi targeting nature, TQ interferes with a wide range of tumorigenic processes and counteracts carcinogenesis, malignant growth, invasion, migration, and angiogenesis. Additionally, TQ can specifically sensitize tumor cells towards conventional cancer treatments (e.g., radiotherapy, chemotherapy, and immunotherapy) and simultaneously minimize therapy-associated toxic effects in normal cells besides being cost effective and safe. TQ was found to play a protective role when given along with chemotherapeutic agents to normal cells. Methods: In the present study, reverse in silico docking approach was used to search for potential molecular targets for cancer therapy. Various metastatic and apoptotic targets were docked with the target ligand. TQ was also tested for its anticancer activities for its ability to cause cell death, arrest cell cycle and ability to inhibit PARP gene expression. Results: In silico docking studies showed that TQ effectively docked metastatic targets MMPs and other apoptotic and cell proliferation targets EGFR. They were able to bring about cell death mediated by apoptosis, cell cycle arrest in the late apoptotic stage and induce DNA damage too. TQ effectively down regulated PARP gene expression which can lead to enhanced cancer cell death. Conclusion: Thymoquinone a neutraceutical can be employed as a new therapeutic agent to target triple negative breast cancer which is otherwise difficult to treat as there are no receptors on them. Can be employed along with standard chemotherapeutic drugs to treat breast cancer as a combinatorial therapy.

scholarly journals EVOLUTION AND VARIATION OF RENIN GENES IN MICE

Genetics ◽  
1984 ◽  
Vol 108 (3) ◽  
pp. 651-667
Author(s):  
Douglas P Dickinson ◽  
Kenneth W Gross ◽  
Nina Piccini ◽  
Carol M Wilson
Keyword(s):  
Gene Expression ◽  
Submandibular Gland ◽  
Regulation Of Gene Expression ◽  
Inbred Strains ◽  
Duplication Event ◽  
Comparative Sequence Analysis ◽  
Chromosome 1 ◽  
Gene Encoding ◽  
Prior Estimate ◽  
Low Levels

ABSTRACT Inbred strains of mice carry Ren-1, a gene encoding the thermostable Renin-1 isozyme. Ren-1 is expressed at relatively low levels in mouse submandibular gland and kidney. Some strains also carry Ren-2, a gene encoding the thermolabile Renin-2 isozyme. Ren-2 is expressed at high levels in the mouse submandibular gland and at very low levels, if at all, in the kidney. Ren-1 and Ren-2 are closely linked on mouse chromosome 1, show extensive homology in coding and noncoding regions and provide a model for studying the regulation of gene expression. An investigation of renin genes and enzymatic activity in wild-derived mice identified several restriction site polymorphisms as well as putative variants in renin gene expression and protein structure. The number of renin genes carried by different subpopulations of wild-derived mice is consistent with the occurrence of a gene duplication event prior to the divergence of M. spretus (2.75-5.5 million yr ago). This conclusion is in agreement with a prior estimate based upon comparative sequence analysis of Ren-1 and Ren-2 from inbred laboratory mice.

scholarly journals Synonymous single nucleotide polymorphism in arsenic (+3) methyltransferase of the Western mosquitofish (Gambusia affinis) and its gene expression among field populations

Ecotoxicology ◽  
2021 ◽  
Author(s):  
Daesik Park ◽  
Catherine R. Propper ◽  
Guangning Wang ◽  
Matthew C. Salanga
Keyword(s):  
Gene Expression ◽  
Sequence Variation ◽  
Allelic Variation ◽  
Arsenic Concentration ◽  
Gambusia Affinis ◽  
Contamination Level ◽  
Water Medium ◽  
Single Nucleotide ◽  
Wide Range ◽  
High Arsenic

AbstractNaturally occurring arsenic is toxic at extremely low concentrations, yet some species persist even in high arsenic environments. We wanted to test if these species show evidence of evolution associated with arsenic exposure. To do this, we compared allelic variation across 872 coding nucleotides of arsenic (+3) methyltransferase (as3mt) and whole fish as3mt gene expression from three field populations of Gambusia affinis, from water sources containing low (1.9 ppb), medium-low (3.3 ppb), and high (15.7 ppb) levels of arsenic. The high arsenic site exceeds the US EPA’s Maximum Contamination Level for drinking water. Medium-low and high populations exhibited homozygosity, and no sequence variation across all animals sampled. Eleven of 24 fish examined (45.8%) in the low arsenic population harbored synonymous single nucleotide polymorphisms (SNPs) in exons 4 and/or 10. SNP presence in the low arsenic population was not associated with differences in as3mt transcript levels compared to fish from the medium-low site, where SNPs were noted; however, as3mt expression in fish from the high arsenic concentration site was significantly lower than the other two sites. Low sequence variation in fish populations from sites with medium-low and high arsenic concentrations suggests greater selective pressure on this allele, while higher variation in the low population suggests a relaxed selection. Our results suggest gene regulation associated with arsenic detoxification may play a more crucial role in influencing responses to arsenic than polymorphic gene sequence. Understanding microevolutionary processes to various contaminants require the evaluation of multiple populations across a wide range of pollution exposures.

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