title: Hes-1, a known transcriptional repressor, acts as a transcriptional activator for the human acid alpha-glucosidase gene in human fibroblast cells.
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 alpha-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.
authors.affiliation: Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Building 10, Room 9N244, 9000 Rockville Pike, Bethesda, Maryland 20892-1820, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
authors.forename: Nina
authors.initials: N
authors.lastname: Raben
authors.forename: Paul H
authors.initials: PH
authors.lastname: Plotz
mesh_terms: D000328:Adult; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D004742:Enhancer Elements, Genetic; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D005087:Glucan 1,4-alpha-Glucosidase / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D010957:Plasmids; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D020218:Response Elements; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D000072056:Transcription Factor HES-1; D014162:Transfection
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005087:Glucan 1,4-alpha-Glucosidase; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D000072056:Transcription Factor HES-1; C078493:HES1 protein, human