The human ACHE extended promoter. An exceptionally long stress-responding promoter controls the human acetylcholinesterase gene expression

M. Shapira*, A. Grant, H. Soreq

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The acetylcholine hydrolyzing enzyme acetylcholinesterase (AChE) is a key element in cholinergic neurotransmission, which is known to be upregulated under acute psychological stress. We have recently reported massive transcriptional activation of ACHE gene expression following forced swim stress; however, the genomic origin(s) of this induction and the extent of individual variability in its intensity remained obscure. To explore the possible causes of these phenomena, we subjected the mammalian ACHE locus, harboring this gene to database searches and transcriptional analyses. Here, we report the properties of an extended promoter domain upstream to the ACHE gene. The 22 Kb long ACHE upstream region was found to be rich in consensus motifs for binding diverse transcription factors, including the stress-associated glucocorticoid receptor, stat5 and the interleukin 6 receptor. The mouse database of expressed sequence tags (EST) includes ACHE mRNA transcripts from several tissues; ESTs from a yet broader range of tissue sources were found that are derived from an adjacent, inversely oriented gene, ARS. Moreover, high resolution in situ hybridization demonstrated that ARS mRNA is expressed at a higher level in hippocampal neurons of human (h)AChE-overexpressing transgenic mice than in FVB/N controls. These findings demonstrate genomic stress response elements in the extended ACHE promoter, and suggest complex multigenic and strain-specific control for this locus.

Original languageEnglish
Pages (from-to)17-21
Number of pages5
JournalItalian Journal of Psychiatry and Behavioural Sciences
Volume10
Issue number1
StatePublished - 2000

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