Copper and MTF1: New roles for a classic metal sensing transcription factor in myogenesis
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ABSTRACT:
PROVIDER: PRJNA478204 | ENA |
REPOSITORIES: ENA
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Project description:MTF1 is a highly conserved metal-binding transcription factor in eukaryotes. MTF1 binds to DNA sequence motifs, termed metal response elements (MREs) to induce the expression of genes involved in metal and oxidative stress homeostasis. MTF1 is responsive to both metal excess and deprivation, and can also protect cells from oxidative and hypoxic stresses. Disruption of metal homeostasis leads to the development of several pathological states. Despite its roles in these processes , MTF1 has been shown to be required for developmental processes such as embryonic liver formation. In this study, we used multiple strategies to understand the mechanism by which MTF1 functions in skeletal muscle differentiation and to determine the role cellular copper (Cu) status plays in this process. We provide the functional relationships between MTF1, Cu, myogenic gene promoters, and MyoD, an specific component of the myogenic transcriptional machinery in differentiating primary myoblasts derived from mouse satellite cells. We found that MTF1 is induced and translocated to the nucleus upon initiation of myogenesis. Consistent with previous studies from our laboratory , addition of non-toxic concentrations of Cu promote myogenesis and enhanced MTF1 expression. CRISPR/Cas9-mediated depletion of MTF1 demonstrated that MTF1 is essential for proper development of skeletal muscle, as partial Mtf1 knockdown leads to apoptosis to differentiating myoblasts. MTF1 was also found to bind Cu at a carboxy-terminal tetra-cysteine cluster, which may contribute to the mobilization of Cu to the nucleus during myogenesis. ChIP-seq and ChIP-qPCR analyses showed that MTF1 binds at the promoter regions of myogenic genes as part of a complex with MyoD, the master transcriptional regulator of the myogenic lineage. These results have the potential to initiate a new area of research in MTF1 function and in the regulation of myogenesis. Furthermore, these studies set the basis to understand the role of Cu at the transcriptional level, affects growth and development and will contribute to the largely unexplored are of muscular phenotypes observed in human pathologies associated to Cu misbalance, such as Menkes’ and Wilson’s diseases.
2019-10-04 | GSE116331 | GEO
Project description:Chemical exposures in fish have been linked to loss of olfaction leading to an inability to detect predators and prey and decreased survival. However, the mechanisms underlying olfactory neurotoxicity are not well characterized, especially in environmental exposures which involve chemical mixtures. We used zebrafish to characterize olfactory transcriptional responses by two model olfactory inhibitors, the pesticide chlorpyrifos (CPF) and mixtures of CPF with the neurotoxic metal copper (Cu).
2013-05-21 | GSE47039 | GEO
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| S-EPMC6894080 | biostudies-literature
Project description:Iron and copper are important environmental nutrients for plant growth. However, the molecular mechanisms of both iron and copper signaling that integrate the two pathways remain poorly understood. The Arabidopsis thaliana high affinity copper transporter COPT5, is a tonoplast localized permease involved in copper remobilization. Here, a global expression microarray analysis of the copt5 mutant points out the induction of iron deficiency responses, including NATURAL RESISTANCE-ASSOCIATED MACROPHAGE PROTEIN 4 (NRAMP4), a tonoplast-localized iron transporter. The copper requirement in iron perception and uptake from the media becomes more evident in the double nramp3nramp4 mutant, unable to remobilize iron from vacuoles, that is highly sensitive to copper deficiency. Furthermore, COPT5 expression is altered under iron deficiency and the copt5 mutant is sensitive to iron deficiency and is unable to perceive iron in the media under copper deficiency. Noteworthy, iron deficiency post-transcriptionally restraints the copper-dependent superoxide dismutase protein levels and the subsequent activity. As a consequence of its increased iron deficiency responses, the copt5 mutant present lower levels of both copper- and iron-dependent superoxide dismutase activities. Moreover, the copt5 mutant mobilizes faster its iron storage pools and presents higher levels of iron in cotyledons and seeds. These results underline the importance of internal metal pools in the understanding of copper and iron deficiency responses and their crosstalk that are critical for governing proper plant development in response to combined metal scarcities in soils.
2017-05-30 | GSE91044 | GEO
Project description:Salmonella can infect a wide range of hosts and survive in the environment. This invasive pathogen has therefore evolved and acquired specific traits to cope with different, and in most cases unfavorable, conditions. In particular, transition metal ions are widely spread in these niches. These ions are essential in biology and play key roles in the structure-function of a large number of proteins. They can also be toxic, especially at high concentrations. Intracellular metal ion concentrations must therefore be tightly controlled to maintain normal metabolism. Salmonella has acquired traits to deal with the presence of toxic concentrations of some of these ions and, at the same time, to fulfill its requirement for essential metal ions when they are scarce. In this work we analyze the transcriptional response of Salmonella enterica to copper and zinc, two of these essential metals, in both rich (SLB) and defined (M9) media and at short times (10 minutes). This tiling-array based work provides a detailed description of the main transcriptional response when Salmonella detects fluctuations in copper and zinc concentrations. 14028s cells were grown up to OD 0.6, then, copper 10 uM (M9) or 1 mM (SLB) or Zn 50uM (M9) or 0.25 mM (SLB) was added and bacteria were grown for 10 minutes, RNA was isolated after this time. The RNA from bacteria grown without metal was also isolated. Each sample was analized by duplicate.
2012-03-15 | E-GEOD-35328 | biostudies-arrayexpress
Project description:Chemical exposures in fish have been linked to loss of olfaction leading to an inability to detect predators and prey and decreased survival. However, the mechanisms underlying olfactory neurotoxicity are not well characterized, especially in environmental exposures which involve chemical mixtures. We used zebrafish to characterize olfactory transcriptional responses by two model olfactory inhibitors, the pesticide chlorpyrifos (CPF) and mixtures of CPF with the neurotoxic metal copper (Cu). 30 one-year-old adult AB strain zebrafish were exposed, in groups of three, to CPF/Cu concentrations of 0/0, 0.1/0, 0.25/0, 0.6/0, 0/0.1, 0/0.25, 0/0.6, 0.1/0.25, 0.25/0.25, 0.6/0.25.
2013-05-21 | E-GEOD-47039 | biostudies-arrayexpress
Project description:Our hypothesis is that copper modulates the activity of multiple intracellular signal transduction pathways to affect transcription. We have previously shown that copper activates transcription through both metal- and oxidative stress-responsive signal transduction pathways. Since the global molecular mechanisms underlying copper toxicity have not been well elucidated in humans, we have profiled transcriptome changes in HepG2 cells exposed to 100, 200, 400 and 600 uM copper for 4, 8, 12 and 24 hours using a human oligonucleotide microarray. Differentially expressed genes were identified, and integrated into biological and functional pathways through Gene Ontology analysis. Global gene expression profile was overlaid onto biomolecular interaction networks and signal transduction cascades using pathway mapping and interactome identification. Keywords: copper toxicity, HepG2 cells, copper concentrations: 100, 200, 400 and 600 uM, exposure times: 4, 8, 12, and 24 h, expression profiles of copper-responsive genes
2009-06-25 | GSE9539 | GEO
Project description:Copper induced stress is known to involve an enhanced oxidant production. This event could be accompanied by an antioxidant response. However, additional processes transcriptionally regulated might participate in the protective response against the metal ions. We used microarrays to detail the global programme of gene expression due to the copper overload and outline the cell processes mostly involved in the toxicity of the metal ions in two cell lines, BEAS-2B cells and HCT116 cells.
2018-11-06 | GSE109375 | GEO
Project description:Salmonella can infect a wide range of hosts and survive in the environment. This invasive pathogen has therefore evolved and acquired specific traits to cope with different, and in most cases unfavorable, conditions. In particular, transition metal ions are widely spread in these niches. These ions are essential in biology and play key roles in the structure-function of a large number of proteins. They can also be toxic, especially at high concentrations. Intracellular metal ion concentrations must therefore be tightly controlled to maintain normal metabolism. Salmonella has acquired traits to deal with the presence of toxic concentrations of some of these ions and, at the same time, to fulfill its requirement for essential metal ions when they are scarce. In this work we analyze the transcriptional response of Salmonella enterica to copper and zinc, two of these essential metals, in both rich (SLB) and defined (M9) media and at short times (10 minutes). This tiling-array based work provides a detailed description of the main transcriptional response when Salmonella detects fluctuations in copper and zinc concentrations.
2012-03-15 | GSE35328 | GEO
Project description:Halobacterium salinarum is a halophillic archea that is capable of sustaining growth despite dramatic changes to the concentration of ions in its extracellular environment. Here we studied H. salinarum's specific adaptation response to the transition metal copper.
2012-06-30 | GSE39028 | GEO