Is RE1/NRSE a common cis-regulatory sequence for ChAT and VAChT genes?
Choline acetyltransferase (ChAT), the biosynthetic enzyme of acetylcholine, and the vesicular acetylcholine transporter (VAChT) are both required for cholinergic neurotransmission. These proteins are encoded by two embedded genes, the VAChT gene lying within the first intron of the ChAT gene. In the nervous system, both ChAT and VAChT are synthesized only in cholinergic neurons, and it is therefore likely that the cell type-specific expression of their genes is coordinately regulated. It has been suggested that a 2336-base pair genomic region upstream from the ChAT and VAChT coding sequences drives ChAT gene expression in cholinergic structures. We investigated whether this region also regulates VAChT gene transcription. Transfection assays showed that this region strongly represses the activity of the native VAChT promoters in non-neuronal cells, but has no major effect in neuronal cells whether or not they express the endogenous ChAT and VAChT genes. The silencer activity of this region is mediated solely by a repressor element 1 or neuron-restrictive silencer element (RE1/NRSE). Moreover, several proteins, including RE1-silencing transcription factor or neuron-restrictive silencer factor, are recruited by this regulatory sequence. These data suggest that this upstream region and RE1/NRSE co-regulate the expression of the ChAT and VAChT genes.
De Gois
S
S
Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, CNRS, UMRC 9923, Bâtiment CERVI, Hôpital de la Pitié Salpêtrière, 83, boulevard de l'Hôpital, 75013 Paris, France.
Houhou
L
L
Oda
Y
Y
Corbex
M
M
Pajak
F
F
Thévenot
E
E
Vodjdani
G
G
Mallet
J
J
Berrard
S
S
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002795:Choline O-Acetyltransferase / Q000235:genetics*; D005786:Gene Expression Regulation; D007438:Introns; D026901:Membrane Transport Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D009435:Synaptic Transmission / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C493460:Slc18a3 protein, mouse; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; D002795:Choline O-Acetyltransferase