The TFIID Subunit TAF4 Regulates Keratinocyte Proliferation and Has Cell-Autonomous and Non-Cell-Autonomous Tumor Suppressor Activity in Mouse Epidermis

The study investigated the role of the TAF4 subunit of transcription factor TFIID in mouse epidermis. Inactivation of TAF4 in foetal mouse epidermis led to reduced expression of skin barrier function genes and resulted in early neonatal death. In adult mice, TAF4 inactivation caused significant fur loss and disrupted the hair cycle, particularly the anagen phase, while paradoxically increasing the expression of genes normally active during this phase. This indicated a desynchronization of gene expression. Additionally, the adult TAF4 mutant epidermis exhibited hyperplasia and upregulation of EGF family mitogens. Furthermore, TAF4 deficiency facilitated the malignant transformation of chemically induced papillomas and the development of invasive melanocytic tumors. The findings suggest that TAF4 plays a crucial role in regulating keratinocyte proliferation and possesses both cell-autonomous and non-cell-autonomous tumor suppressor functions.