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- Title
A Novel Cis-Acting Element Regulates HES-1 Gene Expression in P19 Embryonal Carcinoma Cells Treated with Retinoic Acid1.
- Authors
Wakabayashi, Nobunao; Kageyama, Ryoichiro; Habu, Toshiyuki; Doi, Toshihide; Morita, Takashi; Nozaki, Masami; Yamamoto, Masayuki; Nishimune, Yoshitake
- Abstract
The regulatory mechanisms of mammalian hairy and Enhancer of split homologue-1 (HES-1) genes were examined in mouse P19 embryonic carcinoma cells (P19 cells). Undifferentiated P19 stem cells expressed a basal level of the HES-1 gene, whereas the expression of this gene was increased upon induction of the cells to a neural cell lineage using retinoic acid (RA). Reporter co-transfection analysis identified an activating region within the upstream promoter region of HES-1 from nucleotides −201 to −172. This activating region, called activating region X (ARX), shows a high GC content and contains both an AP-2 binding motif and a CCAAT box. An electrophoretic mobility shift assay using nuclear proteins extracted from P19 cells showed that ARX forms a specific DNA-protein complex. Importantly, ARX-dependent transcription, as well as ARX-binding activity, was significantly increased in P19 cells treated with RA. These results indicate that ARX transduces signals that up-regulate HES-1 gene expression in response to RA-treatment. Thus, a novel cis-acting element involved in HES-1 gene regulation that plays a role in RA-induced neural differentiation of P19 cells has been identified.
- Subjects
TRETINOIN; MAMMALS; NEURAL cell adhesion molecule; GENE transfection; NUCLEOTIDES
- Publication
Journal of Biochemistry, 2000, Vol 128, Issue 6, p1087
- ISSN
0021-924X
- Publication type
Article
- DOI
10.1093/oxfordjournals.jbchem.a022837