Open AccessZinc‐specific activation of a HeLa cell nuclear protein which interacts with a metal responsive element of the human metallothionein‐II A gene
Author(s) -
KOIZUMI Shinji,
YAMADA Hirotomo,
SUZUKI Kaoru,
OTSUKA Fuminori
Publication year - 1992
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1992.tb17454.x
Subject(s) - metallothionein , zinc , cadmium , zinc finger , activator (genetics) , metalloprotein , hela , microbiology and biotechnology , chemistry , metal , oligonucleotide , gene , transcription factor , biochemistry , biology , cell , organic chemistry
Transcription of metallothionein genes is activated by heavy metals such as zinc and cadmium, and a DNA element called metal responsive element (MRE) is essential for this process. By mobility‐shift assay, we identified a HeLa‐cell nuclear protein which specifically binds to MREa of human metallothionein‐II A gene. This protein, named ZRF (zinc‐regulatory factor), is present in the cells untreated with heavy metals. Zinc is essential for, and increases in a dose‐dependent manner, the binding of ZRF to MREa. Other heavy metals which can also induce metallothioneins, including cadmium, copper and mercury, do not activate ZRF. A MREa‐containing oligonucleotide that can bind ZRF confers heavy metal‐inducibility to a heterologous promoter, suggesting that ZRF is a zinc‐dependent transcriptional activator. In addition to the MRE core sequence, the surrounding sequences are also important for both ZRF binding in vitro , and zinc‐dependent transcriptional activation in vivo . MREa by itself responds not only to zinc but also to other metallothionein‐inducing heavy metals, indicating that the ZRF protein, not the MREa sequence, is responsible for the zinc specificity.