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Terminal differentiation of skin keratinocytes, in which the transition from basal keratinocytes to corneocytes is occurred, is a complex process that requires the simultaneous activation and inactivation of a wide variety of genes that must be expressed at the correct time and in the correct location. A number of ubiquitous transcription factors, such as AP1, Sp1, and the AP2 family members, are involved in regulating keratinocyte gene expression and differentiation. Although the functional involvement of many transcription factors in keratinocyte differentiation has been known, however, it is not sufficient to understand the sophisticated regulatory mechanism underlying this process. In this study, additional transcription factors such as Sox9, PITX2 and Brn2 are discussed based on recent research results. When Sox9 was overexpressed, cell growth was enhanced while the expression of differentiation-related genes such as loricrin and involucrin was markedly decreased. In contrast, PITX2c overexpression led to increase of differentiation markers at both mRNA and protein levels. Similarly, Brn2 overexpression resulted in increased expression of the differentiation-related genes. These results indicate that keratinocyte differentiation is a dynamic process in which a variety of transcription factors are coordinately involved to balance the proliferation and differentiation.
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