The Emerging Role of ATP-Dependent Chromatin Remodeling in Memory and Substance Use Disorders

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.

The emerging role of chromatin remodelers in neurodevelopmental disorders: a developmental perspective

“…Furthermore, Smarca1 has been shown to directly bind to the promotor of the FoxG1 gene, suggesting that timed chromatin remodelling by SMARCA1 is essential for controlling neuronal development and differentiation [ 268 ]. Taken together, these results confirm that timed chromatin remodelling of SWI/SNF-remodelers is essential during neurodevelopment [ 272 ]. It is therefore thus not surprising that misexpression of SWI/SNF complex subunits cause NDDs.…”

Decoding cocaine-induced proteomic adaptations in the mouse nucleus accumbens

“…Moreover, the SUMOylation and histone methylation clusters highlighted the importance of SMARCA1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 1), an ISWI (imitation switch) family member. SMARCA1, recognized for its chromatin remodeling capabilities, has been implicated in several neuronal functions, including neurodevelopment, neuronal proliferation, and differentiation ( 46 ). In addition, histone H4 acetylation and histone methylation have both been associated with cocaine action ( 47 , 48 ).…”

General intelligence and executive functioning are overlapping but separable at genetic and molecular pathway levels: An analytical review of existing GWAS findings

“…The two common biological pathways for g and EF constructs, Chromatin organization and Chromatin modifying enzymes , that remained statistically significant at both relaxed p<0.05 and more stringent p<0.01, are of particular interest. For decades, research has implicated epigenetic mechanisms, such as histone modifications in regulating chromatin compaction necessary for experience-dependent changes to gene expression and cell function during memory formation [ 78 , 79 ], however little is known the role epigenetic mechanisms play in general intelligence or/and executive functioning. Our study suggests that chromatin organization molecular processes, which regulate the accessibility of DNA and help to protect it from damage, are related to both g and EF via chromatin modifying enzymes pathway as a regulatory mechanism underlying long-lasting changes in neurons, with direct implications on brain function [ 80 ].…”