Regulation of Cell Differentiation by Sox Family Transcription Fctors

SOX家族转录因子在细胞分化调控中起关键作用。目前已鉴定出20多个SOX家族蛋白，并将其分为A ~ g类，它们具有类似HMG结构域识别的DNA结合共识序列AACAA(A/T)，但其靶基因和调控靶过程在不同组的SOX蛋白之间明显不同。以B组SOX蛋白（SOX 1 ~ 3）为研究对象，研究了SOX蛋白的不同作用机制。SOX1-3 （B1组）参与转录激活，而SOX14和21 （B2组）参与转录抑制，它们在中枢神经系统和感觉器官的基本表达域广泛重叠。SOX2单独不表现出作为转录激活因子的活性，但与伴侣因子联合表达激活电位。在透镜中，SOX2的伴侣因子被鉴定为Pax6， SOX2、Pax6与靶DNA（如delta-crystallin enhancer）形成三元配合物，激发了较高的基因转录活性。这也是晶状体分化产生的机制。这种SOX-partner相互作用可以推广到其他情况，SOX蛋白与其partner因子之间的合作作用是细胞状态遗传开关和细胞分化的核心机制。

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.