Understanding and Augmenting Liver Regeneration by Dissecting Epigenetic Mechanisms
Epigenetic machines reprogram genomic structure, gene expression, and cellular functions during tissue regeneration. It is unknown how this machinery influences regenerative capacity in any tissue system. The liver is the ideal context in which to unravel these longstanding questions. We discovered that Arid1a, a component of the SWI/SNF ATP-dependent chromatin-remodeling complex, plays critical roles in liver injury and regeneration (Sun et al., 2016). Chromatin structure is remodeled during regeneration to alter accessibility for transcription factors that alter cell fate and function such that lost tissues can be replenished. We showed that liver-specific Arid1a knockout mice have enhanced regeneration after multiple forms of surgical, chemical, and genetic injury.
For the first time, these findings connect chromatin-remodeling machinery with organ regeneration and suggest that we have uncovered only the “tip of the iceberg” in terms of understanding the epigenetic mechanisms regulating regeneration. Currently, we are examining how this chromatin-remodeling complex controls gene expression and regeneration on the molecular level.