Regulation of Cell Differentiation by Sox Family Transcription Fctors

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SOX family transcription factors play a key role in regulation of cell differentiation. More than twenty SOX family proteins have been identified and classified into groups A to G. They share the DNA binding consensus sequence AACAA(A/T) recognized by analogous HMG domains, but their target gene and the target process of regulation are clearly distinct between SOX proteins of different groups.Focusing on Group B SOX proteins (SOX 1 to 3), we investigated the mechanisms of distinct actions of the SOX proteins. SOX1-3 (Group B1) are involved in transcriptional activation, while SOX14 and 21 (Group B2) are involved in transcriptional repression, and they overlap extensively in the expression domains in the CNS and in the rudiments of sensory organs. SOX2 alone does not show an activity as transcriptional activator, but in combination with partner factors, it expresses the activation potential.In the lens, the partner factor of SOX2 was identified as Pax6, and the ternary complex formed among SOX2, Pax6 and the target DNA exemplified by delta-crystallin enhancer provoke a high activity of gene transcription. This is also the mechanism to initiate lens differentiation. This SOX-partner interaction can be generalized to other cases, and the cooperative action between a SOX protein and its partner factor is a central mechanism of the genetic switch of the cell state, the cell differentiation.