Library Subscription: Guest
Begell Digital Portal Begell Digital Library eBooks Journals References & Proceedings Research Collections
Critical Reviews™ in Eukaryotic Gene Expression

Impact factor: 1.660

ISSN Print: 1045-4403
ISSN Online: 2162-6502

Critical Reviews™ in Eukaryotic Gene Expression

DOI: 10.1615/CritRevEukarGeneExpr.v19.i4.40
pages 301-317

Human Metallothionein Expression under Normal and Pathological Conditions: Mechanisms of Gene Regulation Based on In silico Promoter Analysis

Debby Laukens
Ghent University
Anouk Waeytens
Department of Pathology, Ghent University, Gent
Pieter De Bleser
Department for Molecular Biomedical Research, Flanders Institute for Biotechnology (VIB); and Department of Molecular Biology, Ghent University, Gent
Claude Cuvelier
Department of Pathology, Ghent University, Gent
Martine De Vos
Department of Gastroenterology, Ghent University, Gent

ABSTRACT

Metallothioneins (MTs) are ubiquitous metal-binding proteins that have been highly conserved throughout evolution. Although their physiological function is not completely understood, they are involved in diverse processes including metal homeostasis and detoxification, the oxidative stress response, inflammation, and cell proliferation. Te human MT gene family consists of at least 18 isoforms, containing pseudogenes as well as genes encoding functional proteins. Most of the MT isoforms can be induced by a wide variety of substances, such as metals, cytokines, and hormones. Different cell types express discrete MT isoforms, which reflects the specifically adapted functions of MTs and a divergence in their regulation. Te aberrant expression of MTs has been described in a number of diseases, including Crohn’s disease, cancer, Alzheimer’s disease, amyotrophic lateral sclerosis, Menkes disease, and Wilson’s disease. Therefore, a thorough understanding of MT gene regulation is imperative. To date, the transcriptional regulation of MTs has primarily been studied in mice. While only four murine MT isoforms exist, the homology between murine and human MTs allows for the evaluation of the regulatory regions in their respective promoters. Here, we review the aberrant expression of MTs in human diseases and the mechanisms that regulate MT1 expression based on an in silico evaluation of transcription factor binding sites.