title: Zinc-controlled gene expression by metal-regulatory transcription factor 1 (MTF1) in a model vertebrate, the zebrafish.
abstract: There is a growing appreciation for the diverse roles of zinc as a signalling substance in biological systems. Zinc signalling is brought about by changes in intracellular concentrations of labile Zn(2+), resulting in both genomic and non-genomic effects. The genomic responses are largely mediated by MTF1 (metal-regulatory transcription factor 1), which binds to MREs (metal-response elements) in the 5' regulatory region of genes in response to zinc. Treatment of cultured zebrafish ZF4 cells with siRNA (small interfering RNA) to MTF1 changed the transcriptional response to zinc for over 1000 genes, as assessed using an oligonucleotide microarray. From this primary list of MTF1-dependent genes, we identified a relatively small cohort that showed a configuration of MREs in their 5' regulatory regions similar to known MTF1 targets. This group showed a remarkable dominance of nucleic acid-binding proteins and other proteins involved in embryological development, implicating MTF1 as a master regulator of gene expression during development.
authors.affiliation: Nutritional Sciences Division, School of Biomedical and Health Sciences, King's College London, Franklin-Wilkins Building, London, UK. christer.hogstrand@kcl.ac.uk
authors.forename: Christer
authors.initials: C
authors.lastname: Hogstrand
authors.forename: Dongling
authors.initials: D
authors.lastname: Zheng
authors.forename: Graham
authors.initials: G
authors.lastname: Feeney
authors.forename: Phil
authors.initials: P
authors.lastname: Cunningham
authors.forename: Peter
authors.initials: P
authors.lastname: Kille
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D053263:Gene Regulatory Networks / Q000187:drug effects; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D023421:Models, Animal; D034741:RNA, Small Interfering / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000235:genetics*; D015032:Zinc / Q000494:pharmacology*; D000097809:Transcription Factor MTF-1
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D008668:Metallothionein; D034741:RNA, Small Interfering; D014157:Transcription Factors; D015032:Zinc; D000097809:Transcription Factor MTF-1; C017800:zinc-binding protein