Genomic and transcriptional characterization of the human ACHE locus: Complex involvement with acquired and inherited diseases

Michael Shapira, Alastair Grant, Mira Korner, Hermona Soreq*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Background: Abnormal levels of the acetylcholinesterase enzyme or aberrations involving the long arm of chromosome 7, harboring the ACHE gene at 7q22, occur in various diseases such as Alzheimer's, Parkinson's, and leukemias. However, the cause(s) of these abnormalities are still unknown. Objective: To search for the genomic elements and transcriptional processes controlling ACHE gene expression and the plausible stability of its locus, by isolating, sequencing and characterizing the human (h)ACHE locus and its mRNA products. Methods: Three clones containing the ACHE gene were isolated from a human chromosome 7 cosmid library. Two of these clones were thereafter sequenced and searched for repetitive elements, open reading frames and corresponding expressed sequence tags. Reverse transcription-polymerase chain reaction was employed to further explore these findings. Results: The locus harboring the G,C-rich ACHE gene was found to be exceptionally rich in Alu repeats. It includes an additional, inversely oriented gene (ARS), tentatively associated with arsenite resistance. EST clones corresponding to both genes were found in cDNA libraries from 11 different human tissue sources, with ARS expressed in 10 additional tissue. Co-regulation of brain ACHE and ARS was suggested from their mutually increased expression following acute psychological stress. Conclusions: The abundance of Alu retrotransposones may predispose the ACHE locus to chromosomal rearrangements. Additionally, coordinated transcriptional regulation is implied from the joint ARS-AChE expression in stress insult responses. Disease-related changes in AChE may therefore reflect locus-specific regulation mechanisms affecting multiple tissues.

Original languageEnglish
Pages (from-to)470-473
Number of pages4
JournalIsrael Medical Association Journal
Volume2
Issue number6
StatePublished - 2000

Keywords

  • Acetylcholinesterase
  • Arsenite resistance
  • Gene locus
  • Inherited diseases
  • Transcriptional activation

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