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.
Bibliographical noteFunding Information:
We thank Drs Andrew Yoo and Vitaly Klyachko for helpful discussions and for critical reading of the manuscript. We thank members of the Cavalli lab for helpful comments. This work was supported in part by grants from NIH ( DE022000 and NS082446 ), and from the University of Missouri Spinal Cord Injuries Research Program (to VC).
ASJC Scopus subject areas
- General Neuroscience