It is becoming increasingly important to understand how epigenetic mechanisms control gene expression during neurodevelopment. Two epigenetic mechanisms that have received considerable attention are DNA methylation and
histone acetylation. Human exome sequencing and genome-wide association studies have linked several neurobiological disorders to genes whose products actively regulate DNA methylation and
histone acetylation. More recently, a third major epigenetic mechanism,
nucleosome remodeling, has been implicated in human developmental and
intellectual disability (ID) disorders.
Nucleosome remodeling is driven primarily through
nucleosome remodeling complexes with specialized
ATP-dependent
enzymes. These
enzymes directly interact with
DNA or
chromatin structure, as well as
histone subunits, to restructure the shape and organization of
nucleosome positioning to ultimately regulate gene expression. Of particular interest is the neuron-specific Brg1/hBrm Associated Factor (nBAF) complex. Mutations in nBAF subunit genes have so far been linked to
Coffin-Siris syndrome (CSS),
Nicolaides-Baraitser syndrome (NBS),
schizophrenia, and
Autism Spectrum Disorder (ASD). Together, these human developmental and ID disorders are powerful examples of the impact of epigenetic modulation on gene expression. This review focuses on the new and emerging role of
nucleosome remodeling in neurodevelopmental and ID disorders and whether
nucleosome remodeling affects gene expression required for cognition independently of its role in regulating gene expression required for development.