title: Positive and negative regulators of the metallothionein gene (review).
abstract: Metallothioneins (MTs) are metal-binding proteins involved in diverse processes, including metal homeostasis and detoxification, the oxidative stress response and cell proliferation. Aberrant expression and silencing of these genes are important in a number of diseases. Several positive regulators of MT genes, including metal-responsive element-binding transcription factor (MTF)-1 and upstream stimulatory factor (USF)-1, have been identified and mechanisms of induction have been well described. However, the negative regulators of MT genes remain to be elucidated. Previous studies from the group of the present review have revealed that the hematopoietic master transcription factor, PU.1, directly represses the expression levels of MT genes through its epigenetic activities, and upregulation of MT results in the potent inhibition of myeloid differentiation. The present review focuses on PU.1 and several other negative regulators of this gene, including PZ120, DNA methyltransferase 3a with Mbd3 and Brg1 complex, CCAAT enhancer binding protein α and Ku protein, and describes the suppression of the MT genes through these transcription factors.
authors.affiliation: Division of Molecular Hematology, Kitasato University Graduate School of Medical Sciences and Division of Hematology, Kitasato University School of Allied Health Sciences, Sagamihara, Kanagawa 252‑0373, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D049109:Cell Proliferation / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D000090205:DNA Methyltransferase 3A; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D008668:Metallothionein / Q000096:biosynthesis / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D051720:Upstream Stimulatory Factors / Q000096:biosynthesis / Q000235:genetics; D000097809:Transcription Factor MTF-1
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D004265:DNA Helicases; D000090205:DNA Methyltransferase 3A; D004268:DNA-Binding Proteins; D008668:Metallothionein; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D051720:Upstream Stimulatory Factors; D000097809:Transcription Factor MTF-1; C000717967:DNMT3A protein, human; C115369:MBD3 protein, human; C116933:PZ120 protein, human; C084108:SMARCA4 protein, human