Ets transcription factors ER81 and Elk1 regulate the transcription of the human presenilin 1 gene promoter.
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). GABPalpha, 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 GABPbeta together with GABPalpha did not increase PS1 transcription. However, GABPbeta alone activated PS1 transcription by two- to threefold. In contrast, the more distantly related Ets factor Elk1 repressed PS1 transcription very effectively.
Pastorcic
Martine
M
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Boulevard, 76107, USA.
Das
Hriday K
HK
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D001483:Base Sequence / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics*; D051268:GA-Binding Protein Transcription Factor; D005786:Gene Expression Regulation / Q000235:genetics; D005809:Genes, Regulator / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D053764:Presenilin-1; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D050807:ets-Domain Protein Elk-1
D016229:Amyloid beta-Peptides; D004268:DNA-Binding Proteins; C494112:ELK1 protein, human; C095239:ETV1 protein, human; D051268:GA-Binding Protein Transcription Factor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1