Zinc-controlled gene expression by metal-regulatory transcription factor 1 (MTF1) in a model vertebrate, the zebrafish

TY - JOUR

T1 - Zinc-controlled gene expression by metal-regulatory transcription factor 1 (MTF1) in a model vertebrate, the zebrafish

AU - Hogstrand, Christer

AU - Zheng, Dongling

AU - Feeney, Graham

AU - Cunningham, Phil

AU - Kille, Peter

PY - 2008

Y1 - 2008

N2 - 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 Zn2+, resulting in both genomic and non-genomic effects. The genomic responses are largely mediated by MTF1 (meta 1-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.

AB - 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 Zn2+, resulting in both genomic and non-genomic effects. The genomic responses are largely mediated by MTF1 (meta 1-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.

U2 - 10.1042/BST0361252

DO - 10.1042/BST0361252

M3 - Article

SN - 1470-8752

VL - 36

SP - 1252

EP - 1257

JO - Biochemical Society Transactions

JF - Biochemical Society Transactions

IS - 6

ER -