Hsf4-KO Mouse

Hsf4, a heat shock factor, is significantly associated with various biological processes and diseases. It is a transcription factor crucial for maintaining cellular homeostasis in response to stress [3]. Mutations in Hsf4 are responsible for congenital cataract formation and it also plays roles in lens terminal differentiation [2].

In maize, ZmHsf4 promotes the heat stress response. ZmHSF20 represses ZmHsf4, and the Zmhsf20 Zmhsf4 double mutant exhibits decreased thermotolerance, indicating ZmHsf4 is downstream of ZmHsf20 in the heat stress response pathway [1].

In HSF4del42 mutant mice, which develop congenital cataracts, there are defects in organelle degradation and autophagic function in lens fibers. HSF4 directly activates the core autophagy protein ATG9a during lens terminal differentiation [2].

In colorectal cancer, HSF4 promotes tumor progression by transactivating c-MET, enhancing the activity of downstream ERK1/2 and AKT signaling pathways [3].

In UV-irradiated skin, HSF4 forms a complex with COIL, which, due to R-loops, regulates the expression of inflammation-related genes [4].

In zebrafish, hsf4 knockout leads to an early-onset cataract with lens developmental defects, including overproliferation of lens epithelial cells and interrupted terminal differentiation of lens fiber cells [5].

In summary, Hsf4 is essential for processes like heat stress response in plants, lens development, autophagy in lens cells, and is involved in disease conditions such as cataract formation and colorectal cancer progression. Gene knockout models in mice and zebrafish have been instrumental in revealing these functions, highlighting the significance of Hsf4 in understanding normal biological processes and disease mechanisms.