PUBLICATION
Dynamic transcriptomic profiles of zebrafish gills in response to zinc depletion
- Authors
- Zheng, D., Kille, P., Feeney, G.P., Cunningham, P., Handy, R.D., and Hogstrand, C.
- ID
- ZDB-PUB-101018-9
- Date
- 2010
- Source
- BMC Genomics 11: 548 (Journal)
- Registered Authors
- Keywords
- none
- Datasets
- GEO:GSE21894
- MeSH Terms
-
- 5' Untranslated Regions/genetics
- Animals
- Binding Sites
- Gene Expression Profiling*
- Gene Expression Regulation*/drug effects
- Gene Regulatory Networks/drug effects
- Genes, Regulator/genetics
- Gills/drug effects
- Gills/metabolism*
- Molecular Sequence Annotation
- Oligonucleotide Array Sequence Analysis
- Protein Binding/drug effects
- Reproducibility of Results
- Reverse Transcriptase Polymerase Chain Reaction
- Signal Transduction/drug effects
- Signal Transduction/genetics
- Time Factors
- Transcription Factors/metabolism
- Zebrafish/genetics*
- Zebrafish/physiology
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Zinc/deficiency*
- Zinc/pharmacology
- PubMed
- 20932299 Full text @ BMC Genomics
- CTD
- 20932299
Citation
Zheng, D., Kille, P., Feeney, G.P., Cunningham, P., Handy, R.D., and Hogstrand, C. (2010) Dynamic transcriptomic profiles of zebrafish gills in response to zinc depletion. BMC Genomics. 11:548.
Abstract
BACKGROUND: Zinc deficiency is detrimental to organisms, highlighting its role as an essential micronutrient contributing to numerous biological processes. To investigate the underlying molecular events invoked by zinc depletion we performed a temporal analysis of transcriptome changes observed within the zebrafish gill. This tissue represents a model system for studying ion absorption across polarised epithelial cells as it provides a major pathway for fish to acquire zinc directly from water whilst sharing a conserved zinc transporting system with mammals.
RESULTS: Zebrafish were treated with either zinc-depleted (water = 2.61 mug L-1; diet = 26 mg kg-1) or zinc-adequate (water = 16.3 mug L-1; diet = 233 mg kg-1) conditions for two weeks. Gill samples were collected at five time points and transcriptome changes analysed in quintuplicate using a 16K oligonucleotide array. Of the genes represented the expression of a total of 333 transcripts showed differential regulation by zinc depletion (having a fold-change greater than 1.8 and an adjusted P-value less than 0.1, controlling for a 10% False Discovery Rate). Down-regulation was dominant at most time points and distinct sets of genes were regulated at different stages. Annotation enrichment analysis revealed that 'Developmental Process' was the most significantly overrepresented Biological Process GO term (P=0.0006), involving 26% of all regulated genes. There was also significant bias for annotations relating to development, cell cycle, cell differentiation, gene regulation, butanoate metabolism, lysine degradation, protein tyrosin phosphatases, nucleobase, nucleoside and nucleotide metabolism, and cellular metabolic processes. Within these groupings genes associated with diabetes, bone/cartilage development, and ionocyte proliferation were especially notable. Network analysis of the temporal expression profile indicated that transcription factors foxl1, wt1, nr5a1, nr6a1, and especially, hnf4a may be key coordinators of the homeostatic response to zinc depletion.
CONCLUSIONS: The study revealed the complex regulatory pathways that allow the organism to subtly respond to the low-zinc condition. Many of the processes affected reflected a fundamental restructuring of the gill epithelium through reactivation of developmental programs leading to stem cell differentiation. The specific regulation of genes known to be involved in development of diabetes provides new molecular links between zinc deficiency and this disease. The present study demonstrates the importance of including the time-dimension in microarray studies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping