TY - JOUR
T1 - Characterization of an acetylcholine receptor α3 gene promoter and its activation by the POU domain factor SCIP/Tst-1
AU - Yang, Xiangdong
AU - McDonough, Jennifer
AU - Fyodorov, Dmitry
AU - Morris, Mark
AU - Wang, Feng
AU - Deneris, Evan S.
PY - 1994/4/8
Y1 - 1994/4/8
N2 - Genes encoding neuronal nicotinic acetylcholine receptors exhibit restricted patterns of expression in the nervous system. We are interested in elucidating the molecular mechanisms responsible for establishing these patterns of expression. This paper presents the characterization of regulatory elements upstream of the neuronal nicotinic acetylcholine receptor α3 gene. We have identified a GC-rich multistart site promoter adjacent to the α3 coding region. Similar α3 start sites were identified in PC12 cells and sympathetic ganglion neurons, suggesting similar control mechanisms in the clonal line and peripheral neurons. The start site region lacks TATA- like sequences but does contain initiator-like sequences. We show, in transient transfection assays, that the POU domain transcription factor, SCIP/Tst-1, specifically activates α3 in a neural context. Other POU domain factors tested only weakly activated or repressed α3. Unexpectedly, we found that α3 basal activity and SCIP/Tst-1 activation of α3 is not dependent on the SCIP/Tst-1 binding sites found upstream of the gene. In addition, mutations in the SCIP/Tst-1 coding region that prevent the factor from binding to DNA with high affinity do not obliterate α3 activation. These results lead us to propose that α3 activation by SCIP/Tst-1 is achieved via protein-protein interactions between SCIP/Tst-1 and a specific complement of transcription factors that act directly on the promoter.
AB - Genes encoding neuronal nicotinic acetylcholine receptors exhibit restricted patterns of expression in the nervous system. We are interested in elucidating the molecular mechanisms responsible for establishing these patterns of expression. This paper presents the characterization of regulatory elements upstream of the neuronal nicotinic acetylcholine receptor α3 gene. We have identified a GC-rich multistart site promoter adjacent to the α3 coding region. Similar α3 start sites were identified in PC12 cells and sympathetic ganglion neurons, suggesting similar control mechanisms in the clonal line and peripheral neurons. The start site region lacks TATA- like sequences but does contain initiator-like sequences. We show, in transient transfection assays, that the POU domain transcription factor, SCIP/Tst-1, specifically activates α3 in a neural context. Other POU domain factors tested only weakly activated or repressed α3. Unexpectedly, we found that α3 basal activity and SCIP/Tst-1 activation of α3 is not dependent on the SCIP/Tst-1 binding sites found upstream of the gene. In addition, mutations in the SCIP/Tst-1 coding region that prevent the factor from binding to DNA with high affinity do not obliterate α3 activation. These results lead us to propose that α3 activation by SCIP/Tst-1 is achieved via protein-protein interactions between SCIP/Tst-1 and a specific complement of transcription factors that act directly on the promoter.
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M3 - Article
C2 - 8144606
AN - SCOPUS:0028237410
SN - 0021-9258
VL - 269
SP - 10252
EP - 10264
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 14
ER -