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PMID:15584924
| Citation |
Wang, TF, Ding, CN, Wang, GS, Luo, SC, Lin, YL, Ruan, Y, Hevner, R, Rubenstein, JL and Hsueh, YP (2004) Identification of Tbr-1/CASK complex target genes in neurons. J. Neurochem. 91:1483-92 |
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| Abstract |
Tbr-1, a neuron-specific T-box transcription factor, plays a critical role in brain development. Here, we performed a computational search using the non-palindromic T-box binding sequence, namely the non-palindromic T-element, to determine the putative downstream target genes of Tbr-1. More than 20 identified genes containing the non-palindromic T-element in the 5' regulatory region were found expressed in brain. Luciferase reporter assays using cultured hippocampal neurons showed that overexpression of Tbr-1 and CASK-enhanced promoter activities of some of these putative target genes, including NMDAR subunit 2b (NR2b), glycine transporter, interleukin 7 receptor (IL-7R) and OX-2. Among these genes, NR2b promoter responded strongest to overexpression of Tbr-1 and CASK. Deletion of the non-palindromic T-elements from NR2b promoter impaired the induction by Tbr-1 and CASK. We also examined expression of these target genes in Tbr-1 knockout mice, it was found that NR2b expression was consistently downregulated. Similarly, both RNA and protein expression levels of NMDAR subunit 1 (NR1), which also contains the non-palindromic T-elements in its 5' regulatory region, were reduced in Tbr-1 knockout mice. We suggest that Tbr-1/CASK protein complex regulates expression of these downstream target genes and thus modulates neuronal activity and function. |
| Links |
PubMed Online version:10.1111/j.1471-4159.2004.02845.x |
| Keywords |
Amino Acid Transport Systems, Neutral/genetics; Animals; Antigens, CD; Antigens, Surface/genetics; Base Sequence; COS Cells; Calcium-Calmodulin-Dependent Protein Kinases/physiology; Cells, Cultured; Cercopithecus aethiops; DNA-Binding Proteins/physiology; Embryo, Mammalian; Gene Expression Regulation; Glycine Plasma Membrane Transport Proteins; Guanylate Kinase; Hippocampus/cytology; Humans; Mice; Mice, Knockout; Molecular Sequence Data; Neurons/metabolism; Promoter Regions, Genetic/physiology; Rats; Receptors, Interleukin-7/genetics; Receptors, N-Methyl-D-Aspartate/genetics |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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