Characterization of an acetylcholine receptor α3 gene promoter and its activation by the POU domain factor SCIP/Tst-1

Xiangdong Yang, Jennifer McDonough, Dmitry Fyodorov, Mark Morris, Feng Wang, Evan S. Deneris

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)10252-10264
Number of pages13
JournalJournal of Biological Chemistry
Volume269
Issue number14
StatePublished - Apr 8 1994
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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