Brain function and chromatin plasticity

Abstract

The characteristics of epigenetic control, including the potential for long-lasting, stable effects on gene expression that outlive an initial transient signal, could be of singular importance for post-mitotic neurons, which are subject to changes with short- to long-lasting influence on their activity and connectivity. Persistent changes in chromatin structure are thought to contribute to mechanisms of epigenetic inheritance. Recent advances in chromatin biology offer new avenues to investigate regulatory mechanisms underlying long-lasting changes in neurons, with direct implications for the study of brain function, behaviour and diseases.

Figure 1. Mechanisms involved in chromatin modifications

Five broad and interrelated mechanisms are known to affect chromatin structure: DNA methylation, histone modification, insertion of histone variants, remodeling complexes, and non-coding RNAs. All five have been shown to be essential contributors to the development and cell fate determination of tissues including in the nervous system, while histone modifications and DNA methylation have so far been more extensively investigated in the context of adult brain function.

Figure 2. Contribution of various chromatin remodeling events throughout life of an organism

Chromatin modifications occurring at different time points during the life of an organism have been associated with various short to long-lasting regulatory events that affect the development and the function of the brain and other tissues.