Abstract
Long-term memory formation requires coordinated regulation of gene expression and persistent changes in cell function. For decades, research has implicated histone modifications in regulating chromatin compaction necessary for experience-dependent changes to gene expression and cell function during memory formation. Recent evidence suggests that another epigenetic mechanism, ATP-dependent chromatin remodeling, works in concert with the histone-modifying enzymes to produce large-scale changes to chromatin structure. This review examines how histone-modifying enzymes and chromatin remodelers restructure chromatin to facilitate memory formation. We highlight the emerging evidence implicating ATP-dependent chromatin remodeling as an essential mechanism that mediates activity-dependent gene expression, plasticity, and cell function in developing and adult brains. Finally, we discuss how studies that target chromatin remodelers have expanded our understanding of the role that these complexes play in substance use disorders.
Highlights
Recent research has advanced our understanding of the molecular infrastructure that facilitates the formation of long-term memories
As histone modifications appear to underlie dysregulated learning in substance use disorder (SUD), the field of neuroepigenetics could benefit from an examination of how other epigenetic mechanisms regulate the molecular, cellular, and circuit-level changes that occur in SUD
The field of neuroscience has acquired a better understanding of how changes to chromatin structure during learning enable stable changes in gene expression, cell function, and memory formation
Summary
Recent research has advanced our understanding of the molecular infrastructure that facilitates the formation of long-term memories. 147 base pairs of genomic DNA are spooled around a histone octamer to form functional chromatin [2] This chromatin is highly compacted in the nucleus, enzymes that control chromatin structure and subsequent access to DNA, play an integral role in regulating gene expression. Recent data have broadened our understanding of the role of chromatin remodeling in MDD and SUDs. In this review, we highlight prominent examples of histone modifications in canonical long-term memory formation and explore how this seminal work provides a framework for understanding the role of other epigenetic mechanisms in the development and reinforcement of SUDs. We discuss chromatin remodeling as an understudied yet robust epigenetic mechanism underlying transcription, cell function, and cognition in the developing and adult brain. We consider how chromatin remodeling complexes (CRCs) may interact with the well-characterized library of histone modifications to induce large-scale changes to chromatin structure and synaptic function in SUDs
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