Dynamic transcriptomic profiles of zebrafish gills in response to zinc depletion

BMC Genomics

Research Article

Phil Cunningham¹  Christer Hogstrand¹  Dongling Zheng²  Richard D Handy³  Peter Kille⁴  Graham P Feeney⁴ 

[1] Mineral Metabolism Group, Nutritional Sciences Division, King's College London, SE1 9NH, London, UK;Mineral Metabolism Group, Nutritional Sciences Division, King's College London, SE1 9NH, London, UK;Division of Infection and Immunity, Windeyer Institute of Medical Sciences, University College London, W1T 4JF, London, UK;School of Biological Sciences, University of Plymouth, PL4 8AA, Plymouth, UK;School of Biosciences, University of Cardiff, CF10 3TL, Cardiff, UK;

关键词: Zinc;    Transcription Factor Binding Site;    Zinc Deficiency;    Zinc Supplementation;    Zinc Uptake;   

DOI  :  10.1186/1471-2164-11-548

 received in 2010-02-10, accepted in 2010-10-08,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundZinc 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.ResultsZebrafish were treated with either zinc-depleted (water = 2.61 μg L-1; diet = 26 mg kg-1) or zinc-adequate (water = 16.3 μg 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.ConclusionsThe 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.

【 授权许可】

Unknown   
© Zheng et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.