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.