Hes-1, a known transcriptional repressor, acts as a transcriptional activator for the human acid α-glucosidase gene in human fibroblast cells

Bo Yan, Nina Raben, Paul H. Plotz

Research output: Contribution to journalArticlepeer-review

Abstract

Hes-1, the mammalian homologue 1 of Drosophila hairy and Enhancer of split proteins, belongs to a family of basic helix-loop-helix proteins that are essential to neurogenesis, myogenesis, hematopoiesis, and sex determination. Hes-1 is a transcriptional repressor for a number of known genes including the human acid α-glucosidase (GAA) gene as we have previously shown in Hep G2 cells. The human GAA gene encodes the enzyme for glycogen breakdown in lysosomes, deficiency of which results in Glycogen Storage Disease type II (Pompe syndrome). Using constructs containing the DNA element that demonstrates repressive activity in Hep G2 cells and conditions in which the same transcription factors, Hes-1 and YY1, bind, we have shown that this element functions as an enhancer in human fibroblasts. Site-directed mutagenesis and overexpression of Hes-1 showed that Hes-1 functions as a transcriptional activator. The dual function of Hes-1 we have found is likely to contribute to the subtle tissue-specific control of this housekeeping gene.

Original languageEnglish (US)
Pages (from-to)582-587
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume291
Issue number3
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Acid α-glucosidase
  • Enhancer
  • Gene expression regulation
  • Glycogen storage disease type II
  • Hes-1
  • Intron

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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