HDAC signaling in neuronal development and axon regeneration

- HDACs function in the differentiation of neuronal progenitor cells to neurons during development as well as in the adult brain.
- HDAC family members have very specific functions: different roles of HDACs are isoform-specific rather than class-specific.
- In injured neurons, HDACs function locally at the site of injury to control cytoskeleton dynamics and in the nucleus to activate a pro-regenerative program.
- HDAC family members emerge as regulatory enzymes in the cytoplasm that can also function independently of their deacetylase activity.

The development and repair of the nervous system requires the coordinated expression of a large number of specific genes. Epigenetic modifications of histones represent an essential principle by which neurons regulate transcriptional responses and adapt to environmental cues. The post-translational modification of histones by chromatin-modifying enzymes histone acetyltransferases (HATs) and histone deacetylases (HDACs) shapes chromatin to adjust transcriptional profiles during neuronal development. Recent observations also point to a critical role for histone acetylation and deacetylation in the response of neurons to injury. While HDACs are mostly known to attenuate transcription through their deacetylase activity and their interaction with co-repressors, these enzymes are also found in the cytoplasm where they display transcription-independent activities by regulating the function of diverse proteins. Here we discuss recent studies that go beyond the traditional use of HDAC inhibitors and have begun to dissect the roles of individual HDAC isoforms in neuronal development and repair after injury.