Positive and negative regulators of the metallothionein gene (review)

Molecular Medicine Reports
Shinichiro Takahashi

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.

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Citations

Sep 9, 2016·International Journal of Molecular Sciences·Xue-Bin LingJi-Ke Li
Apr 14, 2016·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Katharina SchmidtWalter Schaffner
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May 26, 2017·International Journal of Molecular Sciences·Victoria DrechselMartina Höckner
Aug 10, 2019·International Journal of Molecular Sciences·Kuo-Chen HungKuen-Haur Lee
May 17, 2017·Proceedings of the National Academy of Sciences of the United States of America·Cheol-Hee ShinSung-Gil Chi
Nov 28, 2020·Scientific Reports·Ryo KikuokaMasato Asanuma
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May 10, 2021·Environmental Pollution·Milton TalukderJin-Long Li
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