ArticleProceedings of the National Academy of Sciences of the United States of America2000
An initiator element mediates autologous downregulation of the human type A gamma -aminobutyric acid receptor beta 1 subunit gene.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 47 citations in OpenAlex.
- Regulation of Inhibitory Signaling at the Receptor and Cellular Level; Advances in Our Understanding of GABAergic Neurotransmission and the Mechanisms by Which It Is Disrupted in Epilepsy.Frontiers in synaptic neuroscience · 2022Review
- Regulation of GABAMembranes · 2021Review
- Physiological role for GABANature communications · 2021Article
- Nuclear Respiratory Factor 1 (NRF-1) Controls the Activity Dependent Transcription of the GABA-A Receptor Beta 1 Subunit Gene in Neurons.Frontiers in molecular neuroscience · 2018Article
- A role for picomolar concentrations of pregnenolone sulfate in synaptic activity-dependent Ca2+ signaling and CREB activation.Molecular pharmacology · 2014Article
- Polycomblike protein PHF1b: a transcriptional sensor for GABA receptor activity.BMC pharmacology & toxicology · 2013Article
- Brain-derived neurotrophic factor uses CREB and Egr3 to regulate NMDA receptor levels in cortical neurons.Journal of neurochemistry · 2012Article
- Altered Organization of GABA(A) Receptor mRNA Expression in the Depressed Suicide Brain.Frontiers in molecular neuroscience · 2010Article
- Surface expression of GABAA receptors is transcriptionally controlled by the interplay of cAMP-response element-binding protein and its binding partner inducible cAMP early repressor.The Journal of biological chemistry · 2008Article
- Bioinformatic identification of novel putative photoreceptor specific cis-elements.BMC bioinformatics · 2007Article
- In silico comparative genomic analysis of GABAA receptor transcriptional regulation.BMC genomics · 2007Article
- Regionally selective effects of GABA on hypothalamic GABAA receptor mRNA in vitro.Biochemical and biophysical research communications · 2007Article
- Differential gene expression patterns in cyclooxygenase-1 and cyclooxygenase-2 deficient mouse brain.Genome biology · 2007Article
- Egr3 stimulation of GABRA4 promoter activity as a mechanism for seizure-induced up-regulation of GABA(A) receptor alpha4 subunit expression.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
- cAMP response element-binding protein, activating transcription factor-4, and upstream stimulatory factor differentially control hippocampal GABABR1a and GABABR1b subunit gene expression through alternative promoters.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2004Article
- Exonic Sp1 sites are required for neural-specific expression of the glycine receptor beta subunit gene.The Biochemical journal · 2001Article
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3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The regulated expression of type A gamma-aminobutyric acid receptor (GABA(A)R) subunit genes is postulated to play a role in neuronal maturation, synaptogenesis, and predisposition to neurological disease. Increases in GABA levels and changes in GABA(A)R subunit gene expression, including decreased beta1 mRNA levels, have been observed in animal models of epilepsy. Persistent exposure to GABA down-regulates GABA(A)R number in primary cultures of neocortical neurons, but the regulatory mechanisms remain unknown. Here, we report the identification of a TATA-less minimal promoter of 296 bp for the human GABA(A)R beta1 subunit gene that is neuron specific and autologously down-regulated by GABA. beta1 promoter activity, mRNA levels, and subunit protein are decreased by persistent GABA(A)R activation. The core promoter, 270 bp, contains an initiator element (Inr) at the major transcriptional start site. Three concatenated copies of the 10-bp Inr and its immediate 3' flanking sequence produce full neural specific activity that is down-regulated by GABA in transiently transfected neocortical neurons. Taking these results together with those of DNase I footprinting, electrophoretic mobility shift analysis, and 2-bp mutagenesis, we conclude that GABA-induced down-regulation of beta1 subunit mRNAs involves the differential binding of a sequence-specific basal transcription factor(s) to the Inr. The results support a transcriptional mechanism for the down-regulation of beta1 subunit GABA(A)R gene expression and raises the possibility that altered levels of sequence-specific basal transcription factors may contribute to neurological disorders such as epilepsy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.