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Identification of Tbr‐1/CASK complex target genes in neurons
Author(s) -
Wang TingFang,
Ding ChiaNung,
Wang GueyShin,
Luo ShihChi,
Lin YiLing,
Ruan Youlin,
Hevner Robert,
Rubenstein John L. R.,
Hsueh YiPing
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02845.x
Subject(s) - cask , palindromic sequence , gene , biology , protein subunit , promoter , transcription factor , transcription (linguistics) , microbiology and biotechnology , gene expression , palindrome , genetics , crispr , linguistics , philosophy
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.