Structural and functional analysis of the rat metallothionein III genomic locus

Metallothionein III (MT III) has been reported to suppress neuronal growth in a rat in vitro model system. The protein and its specific mRNA are detec ted predominantly in the brain, differentiating MT III from the well-charac terised archetypal metallothioneins. Isolation, sequencing and functional a nalysis of the rat MT III genomic locus indicated that, although the organi sation of the gene was conserved between MT III and the more conventional m etallothioneins, the 5' flanking region of the MT III gene was distinct. Wi thin this region, a number of putative regulatory elements were identified, including the metal regulatory elements (MREs) characteristic of metalloth ionein promoters. However, despite their conservation in sequence with acti ve elements, the MREs of MT III were unresponsive to zinc. A 'silencing ele ment' was revealed within a 250 bp section of the MT III promoter which sup pressed gene expression in two brain cell lines. The operation of this sile ncing region in conjunction with the inactive MREs may explain the distinct expression profile observed for MT III within the central nervous system a nd during neuronal development. (C) 1999 Elsevier Science B.V. All rights r eserved.