TY - JOUR
T1 - Genomic and transcriptional characterization of the human ACHE locus
T2 - Complex involvement with acquired and inherited diseases
AU - Shapira, Michael
AU - Grant, Alastair
AU - Korner, Mira
AU - Soreq, Hermona
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Acetylcholinesterase
KW - Arsenite resistance
KW - Gene locus
KW - Inherited diseases
KW - Transcriptional activation
UR - http://www.scopus.com/inward/record.url?scp=0033839348&partnerID=8YFLogxK
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 10897240
AN - SCOPUS:0033839348
SN - 1565-1088
VL - 2
SP - 470
EP - 473
JO - Israel Medical Association Journal
JF - Israel Medical Association Journal
IS - 6
ER -