Regulation of arsenic methylation: identification of the transcriptional region of the human AS3MT gene

Cell Biol Toxicol. 2022 Oct;38(5):765-780. doi: 10.1007/s10565-021-09611-2. Epub 2021 May 6.

Abstract

The human enzyme As(III) S-adenosylmethionine methyltransferase (AS3MT) catalyzes arsenic biotransformations and is considered to contribute to arsenic-related diseases. AS3MT is expressed in various tissues and cell types including liver, brain, adrenal gland, and peripheral blood mononuclear cells but not in human keratinocytes, urothelial, or brain microvascular endothelial cells. This indicates that AS3MT expression is regulated in a tissue/cell type-specific manner, but the mechanism of transcriptional regulation of expression of the AS3MT gene is not known. In this study, we define the DNA sequence of the core promoter region of the human AS3MT gene. We identify a GC box in the promoter to which the stress-related transcription factor Sp1 binds, indicating involvement of regulatory elements in AS3MT gene expression.

Keywords: AS3MT; Arsenic; Promoter; Transcriptional regulation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Arsenic* / toxicity
  • Endothelial Cells / metabolism
  • Humans
  • Leukocytes, Mononuclear
  • Methylation
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • S-Adenosylmethionine / metabolism
  • Transcription Factors / metabolism

Substances

  • Transcription Factors
  • S-Adenosylmethionine
  • Methyltransferases
  • AS3MT protein, human
  • Arsenic