Beyond transcription factors: the role of chromatin modifying enzymes in regulating transcription required for memory

Abstract

One of the alluring aspects of examining chromatin modifications in the role of modulating transcription required for long-term memory processes is that these modifications may provide transient and potentially stable epigenetic marks in the service of activating and/or maintaining transcriptional processes. These, in turn, may ultimately participate in the molecular mechanisms required for neuronal changes subserving long-lasting changes in behavior. As an epigenetic mechanism of transcriptional control, chromatin modification has been shown to participate in maintaining cellular memory (e.g., cell fate) and may underlie the strengthening and maintenance of synaptic connections required for long-term changes in behavior. Epigenetics has become central to several fields of neurobiology, where researchers have found that regulation of chromatin modification has a significant role in epilepsy, drug addiction, depression, neurodegenerative diseases, and memory. In this review, we will discuss the role of chromatin modifying enzymes in memory processes, as well as how recent studies in yeast genetics and cancer biology may impact the way we think about how chromatin modification and chromatin remodeling regulate neuronal function.

Figure 1.

Modifications of residues on histone H4, H3, H2B, and H2A and their two main functions. (A) This schematic illustrates the basic repeating unit of chromatin, called the nucleosome, which is comprised of a histone octamer that interacts with ∼147 bp of genomic DNA per nucleosome. The histone octamer contains pairs of histone H4, H3, H2B, and H2A. The amino-terminal tails of these core histone proteins are the sites of numerous post-translational modifications (figure adapted from Luger et al. 1997 and Kouzarides 2007). Sites marked with a box are those that have been examined with regard to memory processes. (B) This schematic illustrates the two main functions these histone modifications are thought to perform. On the one hand, they are involved in relaxing physical restraints of compact chromatin structure. On the other hand, they provide docking and recruitment sites for additional factors that contain domains capable of binding specific histone modifications, such as the bromo and chromo domains, which bind acetylated lysines and methylated lysines, respectively.