Glial cell-specific expression of the serotonin 2 receptor gene: selective reactivation of a repressed promoter

Daming Ding, Miklos Toth, Yongzhi Zhou, Christopher Parks, Beth J. Hoffman, Thomas Eugene Shenk

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

The 5′ flanking region of the 5-HT2 receptor gene has been cloned, sequenced and its transcriptional regulatory functions analyzed. The promoter lacks an identifiable TATA motif, and utilizes at least 11 clustered start sites. Promoter function was analyzed by transient assays in rat C6 glioma cells, which were shown to express the endogenous 5-HT2 receptor gene, as well as in rat CREF and human HeLa cells which do not express the endogenous gene. The basal promoter functioned equally well in all three cell lines; and a repression domain, located upstream of the basal promoter, inhibited activity of the promoter in all three cell lines. A far upstream cell specific activator domain restored promoter activity in C6 glioma cells, but did not reactivate the silenced promoter in CREF or HeLa cells. The upstream activator domain, repressor domain and basal promoter functioned in concert to achieve cell type specific expression. The activator domain did not direct C6 glioma cell specific expression in the absence of the repressor domain or in constructs carrying a heterologous basal promoter. These results indicate that glial cell expression of the 5-HT2 receptor gene is achieved through a cell type specific reactivation of a repressed promoter.

Original languageEnglish (US)
Pages (from-to)181-191
Number of pages11
JournalMolecular Brain Research
Volume20
Issue number3
DOIs
StatePublished - Jan 1 1993

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Keywords

  • Gene regulation
  • Glial cell
  • Promoter
  • Reactivation
  • Repression
  • Serotonin 5-HT receptor

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