A cell type-specific silencer in the human choline acetyltransferase gene requiring two distinct and interactive E boxes.
We have previously reported that cholinergic neuron-specific expression of the human choline acetyltransferase gene is mediated by two co-operative silencers. We have now localized the proximal silencer to the region from nucleotide -2195 to -2409, which contains two distinct E boxes (CACCTG and CATGTG). Deletion or mutation of either of these E boxes results in a loss of silencer activity. There are specific nuclear proteins in adrenergic cells which bind to each of the two E boxes. However, nuclear proteins from cholinergic cells only bind the 5' E box not the 3' E box. It is this interaction which appears to be the cause of the inactivity of this silencer in these cells.
Li
Y P
YP
Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas 75235, USA.
Baskin
F
F
Davis
R
R
Wu
D
D
Hersh
L B
LB
D001483:Base Sequence; D002795:Choline O-Acetyltransferase / Q000096:biosynthesis* / Q000235:genetics; D015342:DNA Probes; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009447:Neuroblastoma / Q000235:genetics; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D014407:Tumor Cells, Cultured
D015342:DNA Probes; D002795:Choline O-Acetyltransferase