Coregulation of two embedded gene products, choline acetyltransferase and the vesicular acetylcholine transporter.
The gene encoding the vesicular acetylcholine transporter (VAChT) has recently been localized within the first intron of the gene encoding choline acetyltransferase (ChAT) and is in the same transcriptional orientation. These two genes, whose products are required for the expression of the cholinergic phenotype, could therefore be coregulated. We thus tested the effects on VAChT gene expression of the cholinergic differentiation factor/leukemia inhibitory factor and retinoic acid, both of which induce ChAT activity and increase ChAT mRNA levels in cultured sympathetic neurons. These factors increased both the number of binding sites for vesamicol, a specific ligand of VAChT, and VAChT immunoreactivity. This increase in the number of VAChT molecules resulted from an increase in the amount of VAChT mRNA, as assessed by reverse transcription-PCR and which paralleled that of ChAT mRNAs. These data suggest a functional role for ChAT and VAChT gene organization and are consistent with the existence of a coregulatory mechanism for the embedded ChAT and VAChT genes.
Berrard
S
S
Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, CNRS, Gif sur Yvette, France.
Varoqui
H
H
Cervini
R
R
Israël
M
M
Mallet
J
J
Diebler
M F
MF
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D006131:Growth Inhibitors / Q000494:pharmacology; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology; D026901:Membrane Transport Proteins; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014212:Tretinoin / Q000494:pharmacology; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D026901:Membrane Transport Proteins; D015335:Molecular Probes; D012333:RNA, Messenger; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; D014212:Tretinoin; D002795:Choline O-Acetyltransferase