Abstract
Recent genome-sequencing studies in human neurodevelopmental and psychiatric disorders have uncovered mutations in many chromatin regulators. These human genetic studies, along with studies in model organisms, are providing insight into chromatin regulatory mechanisms in neural development and how alterations to these mechanisms can cause cognitive deficits, such as intellectual disability. We discuss several implicated chromatin regulators, including BAF (also known as SWI/SNF) and CHD8 chromatin remodellers, HDAC4 and the Polycomb component EZH2. Interestingly, mutations in EZH2 and certain BAF complex components have roles in both neurodevelopmental disorders and cancer, and overlapping point mutations are suggesting functionally important residues and domains. We speculate on the contribution of these similar mutations to disparate disorders.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Review
MeSH terms
-
Animals
-
Chromatin / genetics*
-
Chromatin / metabolism
-
Chromatin Assembly and Disassembly
-
Cognition / physiology*
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism
-
Enhancer of Zeste Homolog 2 Protein
-
Histone Deacetylases / genetics
-
Histone Deacetylases / metabolism
-
Humans
-
Intellectual Disability / genetics*
-
Intellectual Disability / pathology
-
Mutation
-
Neurogenesis / genetics*
-
Neurons / physiology
-
Nuclear Proteins / genetics
-
Nuclear Proteins / metabolism
-
Polycomb Repressive Complex 2 / genetics
-
Polycomb Repressive Complex 2 / metabolism
-
Repressor Proteins / genetics
-
Repressor Proteins / metabolism
-
Transcription Factors / genetics
-
Transcription Factors / metabolism
Substances
-
BANF1 protein, human
-
CHD8 protein, human
-
Chromatin
-
DNA-Binding Proteins
-
Nuclear Proteins
-
Repressor Proteins
-
Transcription Factors
-
EZH2 protein, human
-
Enhancer of Zeste Homolog 2 Protein
-
Polycomb Repressive Complex 2
-
HDAC4 protein, human
-
Histone Deacetylases