Chapter 30 - Chromatin Remodeling: Role in Neuropathologies of the Basal Ganglia

Abstract

Publisher Summary This chapter summarizes the general concepts of chromatin remodeling, histone modifications and nucleosomal response, with a particular emphasis on histone acetylation, phosphorylation and methylation, and their dynamic control. Epigenetic mechanisms are key cellular processes that integrate diverse environmental stimuli to exert potent and long lasting changes in gene expression. These mechanisms were initially described in differentiating cells, where a clonal population of cells must decipher the correct transcriptional program from parent to daughter cells. It is now well established that the control of chromatin structure is largely involved in the above the genome cellular process. Chromatin remodeling is a dynamic, cell- and environment-specific process that permits the control of DNA packaging and hence the access to the transcriptional machinery at specific loci. It critically depends on post-translational modifications of histones and integrates diverse external stimuli to exert potent and long lasting changes in gene expression. It reviews how chromatin remodeling can occur in striatal neurons in responses to drugs of abuse, but also in neurological diseases, including HD, dentatorubral-pallidoluysian atrophy (DRPLA) and l-DOPA-induced dyskinesia. The chapter concludes the impor­tance of better understanding the mechanisms that underlie chromatin remodeling to reveal novel drug targets for the development of improved pharmaceutical interventions.