Structure and expression of the human metallothionein genes.

The human metallothioneins are represented by a multigene family consisting of about 14 members. A number of MT-like genes have been isolated from a human genomic library and in this report, four MT genes have been characterized. Our results show that two of these genes represent the MT-I and MT-II processed genes. The other two genes (MT-IF and MT-IG) are functional members of the MT-I gene family. The amino acid sequence encoded by the MT-IF and MT-IG genes differ from the amino acid sequences of the published MT-I proteins at few positions. The 5'-flanking region of these genes contain metal responsive elements. Our studies show that the MT-IF and MT-IG genes are differentially regulated in two human hepatoma cell lines, HepG2 and Hep3B2, and a human lymphoblastoid cell line, WI-L2 in response to the heavy metals cadmium, zinc and copper, and glucocorticoids. In addition, these genes also show cell-type specific expression.