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Nucleic Acids Research, 1992, Vol. 20, No. 1 63-68
© 1992

MOLECULAR BIOLOGY

The expression of the amyloid precursor protein (APP) is regulated by two GC-elements in the promoter

Peter Pollwein, Colin L. Masters1 and Kornard Beyreuther1

Center for Molecular Biology Heidelberg (ZMBH), University of Heidelberg Im Neuenheimer Feld 282, D-6900 Heidelberg, FRG 1Department of Pathology, University of Melbourne Parkville, Victoria 3052, Australia

Received October 15, 1991. Revised December 5, 1991. Accepted December 5, 1991.

The structure of the promoter of the human APP gene resembles that of housekeeping genes, with the presence of a GC-rich region and the lack of a canonical TATA box. Since analysis of the expression of the APP gene, especially at the transcriptional level, might reveal factors or elements, which influence amyloid formation in Alzheimer's disease, a 5' deletion analysis of the APP promoter was performed, leading to the identification of an activating DNA fragment (Ac), acting also on a heterologous promoter. DNasel-footprint analysis revealed three protected regions on the Ac fragment. Further gene transfer experiments showed, that at least two elements, designated A and C, confer transcriptional activity in HeLa cells. Whereas the proximal element A is a 19bp long GC-rich DNA sequence, the distal element C is a GC-palindrome with the sequence 5'GCGGCGCCGC.


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