PMID- 15584924 OWN - NLM STAT- MEDLINE DCOM- 20050121 LR - 20201209 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 91 IP - 6 DP - 2004 Dec TI - Identification of Tbr-1/CASK complex target genes in neurons. PG - 1483-92 AB - 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. FAU - Wang, Ting-Fang AU - Wang TF AD - Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan. FAU - Ding, Chia-Nung AU - Ding CN FAU - Wang, Guey-Shin AU - Wang GS FAU - Luo, Shih-Chi AU - Luo SC FAU - Lin, Yi-Ling AU - Lin YL FAU - Ruan, Youlin AU - Ruan Y FAU - Hevner, Robert AU - Hevner R FAU - Rubenstein, John L R AU - Rubenstein JL FAU - Hsueh, Yi-Ping AU - Hsueh YP LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Amino Acid Transport Systems, Neutral) RN - 0 (Antigens, CD) RN - 0 (Antigens, Surface) RN - 0 (DNA-Binding Proteins) RN - 0 (Glycine Plasma Membrane Transport Proteins) RN - 0 (NR2B NMDA receptor) RN - 0 (Receptors, Interleukin-7) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 0 (T-Box Domain Proteins) RN - 0 (Tbr1 protein, mouse) RN - EC 2.7.11.1 (CASK kinases) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) RN - EC 2.7.4.8 (Guanylate Kinases) RN - UQ4V77A8VA (antigens, CD200) SB - IM MH - Amino Acid Transport Systems, Neutral/genetics MH - Animals MH - Antigens, CD MH - Antigens, Surface/genetics MH - Base Sequence MH - COS Cells MH - Calcium-Calmodulin-Dependent Protein Kinases/*physiology MH - Cells, Cultured MH - Chlorocebus aethiops MH - DNA-Binding Proteins/*physiology MH - Embryo, Mammalian MH - *Gene Expression Regulation MH - Glycine Plasma Membrane Transport Proteins MH - Guanylate Kinases MH - Hippocampus/cytology MH - Humans MH - Mice MH - Mice, Knockout MH - Molecular Sequence Data MH - Neurons/*metabolism MH - Promoter Regions, Genetic/physiology MH - Rats MH - Receptors, Interleukin-7/genetics MH - Receptors, N-Methyl-D-Aspartate/genetics MH - T-Box Domain Proteins EDAT- 2004/12/09 09:00 MHDA- 2005/01/22 09:00 CRDT- 2004/12/09 09:00 PHST- 2004/12/09 09:00 [pubmed] PHST- 2005/01/22 09:00 [medline] PHST- 2004/12/09 09:00 [entrez] AID - JNC2845 [pii] AID - 10.1111/j.1471-4159.2004.02845.x [doi] PST - ppublish SO - J Neurochem. 2004 Dec;91(6):1483-92. doi: 10.1111/j.1471-4159.2004.02845.x.