TY - JOUR
T1 - Glial cell-specific expression of the serotonin 2 receptor gene
T2 - selective reactivation of a repressed promoter
AU - Ding, Daming
AU - Toth, Miklos
AU - Zhou, Yongzhi
AU - Parks, Christopher
AU - Hoffman, Beth J.
AU - Shenk, Thomas
PY - 1993/11
Y1 - 1993/11
N2 - 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.
AB - 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.
KW - Gene regulation
KW - Glial cell
KW - Promoter
KW - Reactivation
KW - Repression
KW - Serotonin 5-HT receptor
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U2 - 10.1016/0169-328X(93)90040-V
DO - 10.1016/0169-328X(93)90040-V
M3 - Article
C2 - 8302156
AN - SCOPUS:0027377333
SN - 0169-328X
VL - 20
SP - 181
EP - 191
JO - Molecular Brain Research
JF - Molecular Brain Research
IS - 3
ER -