Effect of the ubiquitous transcription factors, SP1 and MAZ, on NMDA receptor subunit type 1 (NR1) expression during neuronal differentiation.
The silencer factor NRSF/REST has been reported to restrict expression to neurons of a variety of genes, including that encoding NMDA receptor subunit type 1 (NR1), by suppressing transcription in nonneuronal cells. However, we recently reported that in addition to the absence of NRSF/REST-binding activity, another neuron-specific mechanism is necessary for high level expression of the NR1 gene in neurons. In this study, we explored the mechanism of induction of NR1 promoter activity during neuronal differentiation of the P19 cell line. We identified a 27 base pair GC-rich region in the promoter as an important element responsible for induction of the NR1 gene after neuronal differentiation. We found that the ubiquitous transcription factors SP1 and MAZ bind to this GC-rich region. Surprisingly, the binding activities of SP1 and MAZ are not remarkably changed after neuronal differentiation. Mutations in the SP1 and MAZ sites impair binding of SP1 and MAZ proteins and also decrease NR1 promoter activity. These findings suggest that SP1 and MAZ mediate enhancement of NR1 promoter activity during neuronal differentiation despite the fact that their binding activity does not change.
Okamoto
Shu-ichi
S
Center for Neuroscience and Aging, The Burnham Institute, La Jolla, CA 92037, USA.
Sherman
Katerina
K
Bai
Guang
G
Lipton
Stuart A
SA
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D004268:DNA-Binding Proteins; D020862:GC Rich Sequence / Q000235:genetics; D051379:Mice; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics* / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000235:genetics*; D009435:Synaptic Transmission / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; C076035:c-MYC-associated zinc finger protein