Search results for "Transcription"
showing 10 items of 2278 documents
DeepSRE: Identification of sterol responsive elements and nuclear transcription factors Y proximity in human DNA by Convolutional Neural Network anal…
2021
SREBP1 and 2, are cholesterol sensors able to modulate cholesterol-related gene expression responses. SREBPs binding sites are characterized by the presence of multiple target sequences as SRE, NFY and SP1, that can be arranged differently in different genes, so that it is not easy to identify the binding site on the basis of direct DNA sequence analysis. This paper presents a complete workflow based on a one-dimensional Convolutional Neural Network (CNN) model able to detect putative SREBPs binding sites irrespective of target elements arrangements. The strategy is based on the recognition of SRE linked (less than 250 bp) to NFY sequences according to chromosomal localization derived from …
Posttranscriptional RNA Modifications: Playing Metabolic Games in a Cell’s Chemical Legoland
2014
Nature combines existing biochemical building blocks, at times with subtlety of purpose. RNA modifications are a prime example of this, where standard RNA nucleosides are decorated with chemical groups and building blocks that we recall from our basic biochemistry lectures. The result: a wealth of chemical diversity whose full biological relevance has remained elusive despite being public knowledge for some time. Here, we will highlight a number of modifications that, because of their chemical intricacy, rely on seemingly unrelated pathways to provide co-factors for their synthesis. Besides their immediate role in affecting RNA function, modifications may act as sensors and transducers of i…
Changing fate
2020
Abstract The alpha-secretase A disintegrin and metalloproteinase 10 (ADAM10) and the beta-secretase beta-APP cleaving enzyme 1 (BACE-1) compete in neurons to cleave the amyloid precursor protein (APP). The reaction started by BACE-1, designated the amyloidogenic pathway, leads to formation of neurotoxic amyloid beta peptides (A-betas), while alpha-secretase prevents this and gives rise to an alternative cleavage product (APPs-alpha, nonamyloidogenic pathway). The latter is also known to have neurotrophic and neuroprotective properties. Therefore, identification of mechanisms that lead to a switch in APP processing from the amyloidogenic to the nonamyloidogenic pathway is an attractive avenu…
Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications
2017
Mitochondria play a key role in maintaining cellular metabolic homeostasis. These organelles have a high plasticity and are involved in dynamic processes such as mitochondrial fusion and fission, mitophagy and mitochondrial biogenesis. Type 2 diabetes is characterised by mitochondrial dysfunction, high production of reactive oxygen species (ROS) and low levels of ATP. Mitochondrial fusion is modulated by different proteins, including mitofusin-1 (MFN1), mitofusin-2 (MFN2) and optic atrophy (OPA-1), while fission is controlled by mitochondrial fission 1 (FIS1), dynamin-related protein 1 (DRP1) and mitochondrial fission factor (MFF). PARKIN and (PTEN)-induced putative kinase 1 (PINK1) partici…
Fas signaling-mediated T
2018
Fas induces apoptosis in activated T cell to maintain immune homeostasis, but the effects of non-apoptotic Fas signaling on T cells remain unclear. Here we show that Fas promotes TH9 cell differentiation by activating NF-κB via Ca2+-dependent PKC-β activation. In addition, PKC-β also phosphorylates p38 to inactivate NFAT1 and reduce NFAT1-NF-κB synergy to promote the Fas-induced TH9 transcription program. Fas ligation exacerbates inflammatory bowel disease by increasing TH9 cell differentiation, and promotes antitumor activity in p38 inhibitor-treated TH9 cells. Furthermore, low-dose p38 inhibitor suppresses tumor growth without inducing systemic adverse effects. In patients with tumor, rel…
T-bet as a possible therapeutic target in autoimmune disease
2002
The prominent role of pro-inflammatory cytokines produced by T helper-1 (T(H1)) cells in regulating autoimmune responses in vitro and in vivo has been demonstrated. Recent observations of T cell polarisation by regulatory transcription factors--especially T-bet (T-box expressed in T cells)--raise the question of their influence in controlling autoimmune diseases. Here, the authors summarise recent observations of the role of T-bet in controlling chronic inflammatory and autoimmune diseases and discuss the implications of these findings for future therapeutic approaches.
Identification of novel peroxisome proliferator-activated receptor alpha (PPARalpha) target genes in mouse liver using cDNA microarray analysis.
2001
Peroxisome proliferators, which function as peroxisome proliferator-activated receptor-alpha (PPARalpha) agonists, are a group of structurally diverse nongenotoxic hepatocarcinogens including the fibrate class of hypolipidemic drugs that induce peroxisome proliferation in liver parenchymal cells. Sustained activation of PPARalpha by these agents leads to the development of liver tumors in rats and mice. To understand the molecular mechanisms responsible for the pleiotropic effects of these agents, we have utilized the cDNA microarray to generate a molecular portrait of gene expression in the liver of mice treated for 2 weeks with Wy-14,643, a potent peroxisome proliferator. PPARalpha activa…
Listeria monocytogenes Differential Transcriptome Analysis Reveals Temperature-Dependent Agr Regulation and Suggests Overlaps with Other Regulons
2012
Listeria monocytogenes is a ubiquitous, opportunistic pathogenic organism. Environmental adaptation requires constant regulation of gene expression. Among transcriptional regulators, AgrA is part of an auto-induction system. Temperature is an environmental cue critical for in vivo adaptation. In order to investigate how temperature may affect AgrA-dependent transcription, we compared the transcriptomes of the parental strain L. monocytogenes EGD-e and its Delta agrA mutant at the saprophytic temperature of 25 degrees C and in vivo temperature of 37 degrees C. Variations of transcriptome were higher at 37 degrees C than at 25 degrees C. Results suggested that AgrA may be involved in the regu…
Iron regulatory mechanisms in Saccharomyces cerevisiae
2020
Iron is an essential micronutrient for all eukaryotic organisms because it participates as a redox cofactor in many cellular processes. However, excess iron can damage cells since it promotes the generation of reactive oxygen species. The budding yeast Saccharomyces cerevisiae has been used as a model organism to study the adaptation of eukaryotic cells to changes in iron availability. Upon iron deficiency, yeast utilizes two transcription factors, Aft1 and Aft2, to activate the expression of a set of genes known as the iron regulon, which are implicated in iron uptake, recycling and mobilization. Moreover, Aft1 and Aft2 activate the expression of Cth2, an mRNA-binding protein that limits t…