PUBLICATION
Inhibition of endogenous MTF-1 signaling in zebrafish embryos identifies novel roles for MTF-1 in development
- Authors
- O'Shields, B., McArthur, A.G., Holowiecki, A., Kamper, M., Tapley, J., Jenny, M.J.
- ID
- ZDB-PUB-140513-107
- Date
- 2014
- Source
- Biochimica et biophysica acta. Molecular cell research 1843(9): 1818-33 (Journal)
- Registered Authors
- Keywords
- Embryonic development, MTF-1, Metal, Zebrafish, Zinc homeostasis
- Datasets
- GEO:GSE51298
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Cadmium/toxicity
- Cloning, Molecular
- DNA-Binding Proteins/chemistry
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism*
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism*
- Embryonic Development/drug effects
- Embryonic Development/genetics
- Female
- Gene Expression Profiling
- Gene Expression Regulation, Developmental/drug effects
- Gene Ontology
- Hemopexin/genetics
- Hemopexin/metabolism
- Humans
- Male
- Mice
- Models, Biological
- Molecular Sequence Data
- Mutation/genetics
- Oligonucleotide Array Sequence Analysis
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Reproducibility of Results
- Signal Transduction*/drug effects
- Signal Transduction*/genetics
- Transcription Factors/chemistry
- Transcription Factors/genetics
- Transcription Factors/metabolism*
- Transcriptional Activation/drug effects
- Transcriptional Activation/genetics
- Zebrafish/embryology*
- Zebrafish/genetics*
- PubMed
- 24751692 Full text @ BBA Molecular Cell Research
Citation
O'Shields, B., McArthur, A.G., Holowiecki, A., Kamper, M., Tapley, J., Jenny, M.J. (2014) Inhibition of endogenous MTF-1 signaling in zebrafish embryos identifies novel roles for MTF-1 in development. Biochimica et biophysica acta. Molecular cell research. 1843(9):1818-33.
Abstract
The metal responsive element-binding transcription factor-1 (MTF-1) responds to changes in cellular zinc levels caused by zinc exposure or disruption of endogenous zinc homeostasis by heavy metals or oxygen-related stress. Here we report the functional characterization of a complete zebrafish MTF-1 in comparison with the previously identified isoform lacking the highly conserved cysteine-rich motif (Cys-X-Cys-Cys-X-Cys) found in all other vertebrate MTF-1 orthologs. In an effort to develop novel molecular tools, a constitutively nuclear dominant-negative MTF-1 (dnMTF-1) was generated as tool for inhibiting endogenous MTF-1 signaling. The in vivo efficacy of the dnMTF-1 was determined by microinjecting in vitro transcribed dnMTF-1 mRNA into zebrafish embryos (1-2 cell stage) followed by transcriptomic profiling using an Agilent 4x44K array on 28- and 36-hpf embryos. A total of 594 and 560 probes were identified as differentially expressed at 28hpf and 36hpf, respectively, with interesting overlaps between timepoints. The main categories of genes affected by the inhibition of MTF-1 signaling were: nuclear receptors and genes involved in stress signaling, neurogenesis, muscle development and contraction, eye development, and metal homeostasis, including novel observations in iron and heme homeostasis. Finally, we investigate both the transcriptional activator and transcriptional repressor role of MTF-1 in potential novel target genes identified by transcriptomic profiling during early zebrafish development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping