Fig. 4: Coordinated or balanced activities of HIRA and DAXX in physiology and pathology.

a, b HIRA and DAXX achieve a common goal despite targeting different genomic loci for H3.3 deposition. Such coordinately regulated H3.3 distribution by HIRA and DAXX maintains diverse cellular functions, including development and neuronal activity (a). In addition, HIRA and DAXX collaborate to prevent the development of diseases, including cardiac and neurodegenerative diseases (b). c, d In certain cellular contexts, the delicate balance between HIRA and DAXX is needed for normal physiology, and the disruption of the equilibrium can give rise to various pathological outcomes. For instance, HIRA and DAXX limit differentiation toward erythroid or myeloid lineages, respectively, maintaining the balance of hematopoiesis (c). Dysregulation of either HIRA or DAXX can result in hematological abnormalities. Furthermore, HIRA promotes oncogenesis by upregulating EMT, whereas DAXX acts as a tumor suppressor by protecting telomeres, retrotransposons, and DNA damage responses (DDR), demonstrating their competitive functions (d).