The NMDA (N-methyl-D-aspartate) receptors are important in the regulation of neuronal development, synaptic plasticity, learning and memory, and are involved in several brain pathologies. The NR1 subunit is essential for the assembly of functional receptors, as it forms the calcium-permeable ion channel and contains the obligatory co-agonist binding site. Previous studies have shown that NR1 gene (Grin1) expression is up-regulated during neuronal differentiation and its expression is widespread in the central nervous system. We have previously cloned the chicken Grin1 gene and 1.9 kb of the 5′-regulatory region. In the present study, we analysed the molecular mechanisms that regulate chicken Grin1 gene transcription in undifferentiated cells and neurons. By functional analysis of chicken Grin1–luciferase gene 5′-regulatory region constructs, we demonstrate that the basal promoter is delimited within 210 bp upstream from the main transcription initiation site. DNA–protein binding and functional assays revealed that the 5′-UTR (untranslated region) has one consensus NRSE (neuron-restrictive silencing element) that binds NRSF (neuron-restrictive silencing factor), and one SP (stimulating protein transcription factor) element that binds SP3, both repressing Grin1 gene transcription in undifferentiated P19 cells (embryonic terato-carcinoma cells) and PC12 cells (phaeochromocytoma cells). The promoter region lacks a consensus TATA box, but contains one GSG/SP (GSG-like box near a SP-consensus site) that binds SP3 and up-regulates gene transcription in embryonic chicken cortical neurons. Taken together, these results demonstrate a dual role of SP3 in regulating the expression of the Grin1 gene, by repressing transcription in the 5′-UTR in undifferentiated cells as well as acting as a transcription factor, increasing Grin1 gene transcription in neurons.
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August 11 2008
Transcription of the chicken Grin1 gene is regulated by the activity of SP3 and NRSF in undifferentiated cells and neurons
Gabriel Moreno-González;
Gabriel Moreno-González
*Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Nacional Autónoma de México, Distrito Federal, 04510, México
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Ana María López-Colomé;
†Departamento de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Distrito Federal, 04510, México
1To whom correspondence should be addressed (email [email protected]).
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Gabriela Rodríguez;
Gabriela Rodríguez
*Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Nacional Autónoma de México, Distrito Federal, 04510, México
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Angel Zarain-Herzberg
Angel Zarain-Herzberg
1
*Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Nacional Autónoma de México, Distrito Federal, 04510, México
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
June 06 2008
Accepted:
June 16 2008
Accepted Manuscript online:
June 16 2008
Online ISSN: 1573-4935
Print ISSN: 0144-8463
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biosci Rep (2008) 28 (4): 177–188.
Article history
Received:
June 06 2008
Accepted:
June 16 2008
Accepted Manuscript online:
June 16 2008
Citation
Gabriel Moreno-González, Ana María López-Colomé, Gabriela Rodríguez, Angel Zarain-Herzberg; Transcription of the chicken Grin1 gene is regulated by the activity of SP3 and NRSF in undifferentiated cells and neurons. Biosci Rep 1 August 2008; 28 (4): 177–188. doi: https://doi.org/10.1042/BSR20080058
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