TOX3 regulates calcium-dependent transcription in neurons.
Learning is an essential component of the human brain function. The molecular basis of learning depends on the rapid and stringent regulation of gene expression. We characterized a new member, TOX3 (high mobility box family member 3) of the activity-dependent transcription regulators. We found that TOX3 is activated by calcium and regulates the activation of the immediate early gene, Fos. The implication our work is the discovery of a new regulator in learning and memory.
We report the cloning and characterization of TOX3, a high mobility group box protein involved in mediating calcium-dependent transcription. TOX3 was identified as a calcium-dependent transactivator using the Transactivator Trap screen. We find that TOX3 interacts with both cAMP response element (CRE)-binding protein (CREB) and CREB-binding protein (CBP), and knockdown of the endogenous TOX3 by RNAi leads to significant reduction of calcium-induced c-fos expression and complete inhibition of calcium activation of the c-fos promoter. The effects of TOX3 on calcium-dependent transcription require the CRE elements. These observations identify TOX3 as an important regulator of calcium-dependent transcription and suggest that TOX3 exerts its effect on CRE-mediated transcription via its association with the CREB-CBP complex.