title: Genomic and transcriptional characterization of the human ACHE locus: complex involvement with acquired and inherited diseases.
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 tissues. 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.
authors.affiliation: Department of Biological Chemistry, Hebrew University of Jerusalem, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Shapira
authors.forename: A
authors.initials: A
authors.lastname: Grant
authors.forename: M
authors.initials: M
authors.lastname: Korner
authors.forename: H
authors.initials: H
authors.lastname: Soreq
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics*; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7; D016678:Genome; D006801:Humans; D014158:Transcription, Genetic
chemical_list: D000110:Acetylcholinesterase