Mechanisms of Heavy Metal Sensing by Metal Response Element-binding Transcription Factor-1

Abstract

Heavy metal homeostasis and detoxification systems are often regulated by changes in gene transcription. In higher eukaryotes, metal response element (MRE)-binding transcription factor-1 (MTF-1) is the only known metal-sensing transcription factor and zinc is the only heavy metal which can reversibly and directly activate the DNA-binding activity of MTF-1, leading to its nuclear retention, promoter binding and induction or repression of transcription. Although, cadmium, copper and oxidative stresses can cause the activation of the DNA-binding activity of MTF-1 in vivo, they apparently do so, at least in part, by causing the redistribution of intracellular zinc. MTF-1-dependent metal-sensing transcription mechanisms are not fully understood but clearly involve zinc binding to its unique zinc finger domain. Recently, zinc has been shown to induce the formation of a co-activator complex containing MTF-1 and the histone acetyltransferase p300 which plays an essential role in the activation of mouse metallothionein-I (MT-I) gene transcription. In this review, we focus on current understanding of the mechanisms by which MTF-1 senses heavy metals and activates gene expression.

Effects of zinc methionine supplementation on laying performance, zinc status, intestinal morphology, and expressions of zinc transporters' mRNA in laying hens

“…33 MTs are cysteine-rich, small molecular mass metal-binding proteins 11 that have been proposed to possess several physiological roles, including antioxidant action and homeostasis of essential metals like Zn and copper. 34,35 MTF-1, acting as a cellular Zn sensor, 36 increases ZnT1 and MT transcription by binding metal-responsive elements in response to excessive Zn. 37 In the present study, the expressions of Zip4, ZnT1, ZnT5, MTF-1, and DMT1 mRNA were not significant in duodenum and jejunum of laying hens among all groups.…”

Alteration of DNA binding activity of transcription factors in NRK-52E rat proximal tubular cells treated with cadmium

“…1A and Table 1). MRE is a metal response element on which MTF-1 is induced to bind by Cd (Zhang et al, 2003;Kimura et al, 2009). Increased binding activity to MRE may be primarily due to the activated MTF-1.…”

Rotifers enriched with iodine, copper and manganese had no effect on larval cod (Gadus morhua) growth, mineral status or redox system gene mRNA levels

“…MTs are low molecular weight, cysteine‐rich metal‐binding proteins, which are implicated in both metal storage and detoxification (Nordberg ). Among others, vertebrate mt mRNA transcription is upregulated by increased cellular Zn, Cu and oxidative stress (Culotta & Hamer ; Andrews ; Kimura, Itoh & Andrews ). Thus, in this study, increased mt mRNA expression in larvae fed increased Cu may be a regulatory response to increased cellular Cu levels, perhaps enhancing the ability to bind, transport and excrete Cu from the body.…”