Daxx-flox Mouse

DAXX, also known as Death-domain associated protein 6, is a multifunctional protein involved in numerous cellular processes. It forms a histone H3.3 chaperone complex with ATRX, playing a crucial role in chromatin regulation, including histone deposition and chromatin remodeling. DAXX is associated with pathways such as the p53-related DNA damage response, transcription regulation, and telomere maintenance, and is of great biological importance in processes like mammalian early development and cancer-related events [1,2,3,5]. Genetic models, especially knockout models, are valuable for studying DAXX's functions.

In DAXX and ATRX knockout U87-T cells with ALT-like features, there are defects in p53 chromatin binding and DNA damage response, as well as genome-wide reduction in p53 DNA-binding and chromatin accessibility at p53 response elements. These cells also show depletion of histone H3.3 and accumulation of γH2AX at p53 sites, indicating that loss of DAXX can compromise p53-related functions in ALT-like cells [1]. DAXX depletion in cancer-related studies attenuates lipogenic gene expression, lipogenesis, and tumor growth, as DAXX promotes lipogenesis by interacting with SREBP1 and SREBP2 to activate SREBP-mediated transcription [4]. In mammalian oocytes and early embryos, loss of DAXX affects ATRX recruitment, transcription of tandem repeats and telomere functions, decreasing early embryo viability [5].

In conclusion, DAXX is essential for chromatin-related functions, DNA damage response, and lipogenesis. Gene knockout models have revealed its roles in cancer-related processes and mammalian early development. Understanding DAXX through these models provides insights into disease mechanisms, especially in cancer and early embryonic development, potentially guiding new therapeutic strategies.