Ets transcription factors ER81 and Elk1 regulate the transcription of the human presenilin 1 gene promoter

Martine Pastorcic, Hriday K. Das

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

We have previously defined a crucial DNA element controlling 90% of the expression of the presenilin 1 gene at (-35 to +6). This region contains an Ets transcription factor binding motif, and a 2-base pair alteration within the core sequence (GGAA to TTAA) of the Ets consensus also reduced transcription by over 90%. We have shown that Ets1/2 transcription factors bind specifically to the -10 Ets element and activate PS1 transcription. The identification of other transcription factors recognizing specifically this promoter area should provide insights into the regulation of PS1. We have used the -10 Ets element as a bait in yeast one hybrid screening of a human brain cDNA library. This assay selected three factors from the Ets family: Ets2, ER81 and Elk1. We show that in vitro translated ER81 indeed binds specifically to the -10 region of the PS1 promoter and that ER81 activates by two- to threefold the basal transcription of a presenilin-1 promoter-chloramphenicol acetyltransferase reporter synthetic gene (-119, +178)PS1CAT in transient infection assays in neuroblastoma cells (SK-N-SH). GABPα, a member of the Ets family closely related to Ets2 and also containing a pointed domain, only increased PS1 transcription by about twofold. Cotransfection of GABPβ together with GABPα did not increase PS1 transcription. However, GABPβ alone activated PS1 transcription by two- to threefold. In contrast, the more distantly related Ets factor Elk1 repressed PS1 transcription very effectively.

Original languageEnglish
Pages (from-to)57-66
Number of pages10
JournalMolecular Brain Research
Volume113
Issue number1-2
DOIs
StatePublished - 12 May 2003

Keywords

  • ER81
  • Elk 1
  • Ets factor
  • Presenilin
  • Transcription

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