Author/Editor     Krainc, Dimitri; Bai, Guang; Okamoto, Shu-ichi; Carles, Maria; Kusiak, John W; Brent, Roger N; Lipton, Stuart A
Title     Synergistic activation of the N-methyl-D-aspartate receptor subunit 1 promoter by myocyte enhancer factor 2C and Sp1
Type     članek
Source     J Biol Chem
Vol. and No.     Letnik 273, št. 40
Publication year     1998
Volume     str. 26218-24
Language     eng
Abstract     The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor plays important roles in neuronal development, plasticity, and cell death. NMDA receptor subunit 1 (NR1) is an essential subunit of the NMDA receptor and is developmentally expressed in postnatal neurons of the central nervous system. Here we identify on the NR1 promoter a binding site for myocyte enhancer factor 2C (MEF2C), a developmentally expressed neuron/muscle transcription factor found in cerebrocortical neurons, and study its regulation of the NR1 gene. Co-expression of MEF2C and Sp1 cDNAs in primary neurons or cell lines synergistically activates the NR1 promoter. Disruption of the MEF2 site or the MEF2C DNA binding domain moderately reduces this synergism. Mutation of the Sp1 sites or the activation domains of Sp1 protein strongly reduces the synergism. Results of yeast two-hybrid and co-immunoprecipitation experiments reveal a physical interaction between MEF2C and Sp1 proteins. The MEF2C DNA binding domain is sufficient for this interaction. Dominant-negative MEF2C interferes with expression of NR1 mRNA in neuronally differentiated P19 cells. Growth factors, including epidermal growth factor and basic fibroblast growth factor, can up-regulate NR1 promoter activity in stably transfected PC12 cells, even in the absence of the MEF2 site, but the Sp1 sites are necessary for this growth factor regulation, suggesting that Sp1 sites may mediate these effects.
Descriptors     BINDING SITES
CELL LINE
DNA-BINDING PROTEINS
GENE EXPRESSION REGULATION, DEVELOPMENTAL
MYOGENIC REGULATORY FACTORS
NERVE TISSUE PROTEINS
NUCLEAR PROTEINS
PROTEIN BINDING
RNA, MESSENGER
RECEPTORS, N-METHYL-D-ASPARTATE