Cited by 544Genetics and Neurodevelopmental DisordersChromatin Remodeling and CancerGenomics and Chromatin Dynamics

From neural development to cognition: unexpected roles for chromatin

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Ronan, Jehnna L., Wu, Wei, Crabtree, Gerald R.·2013·Nature Reviews Genetics

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.

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  • By comparing these genes with intellectual disability genes, that study identified molecular processes preferentially disrupted by ASD risk genes, including transcriptional regulation, chromatin regulation and synaptic development, and disruption of BAF (SWI/SNF) complex-mediated neuronal development.

    “By comparing these genes with genes that cause intellectual disability, this study identified molecular processes that are preferentially disrupted by ASD risk genes, including transcriptional regulation, chromatin regulation and synaptic development, and it identified disruption of specific pathways, such as BAF (SWI/ SNF) complex-mediated neuronal development 30,110,111.”
  • BAF complexes are ATP-dependent chromatin remodeling complexes consisting of 15 subunits, including one of the ATPase core subunits SMARCA4 or SMARCA2.

    “These ATP-dependent chromatin remodelling complexes consist of 15 subunits, including one of both ATPase core subunits SMARCA4 or SMARCA237.”

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1 of the 130 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. [7]Allis CD Jenuwein T Reinberg D Epigenetics Cold Spring Harbor Laboratory Press 2007
  2. [102]Kadoch C Hargreaves D Hodges C Crabtree GR Nature Genet (in the press)

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Authors
Ronan, J. L., Wu, W., & Crabtree, G. R.
Affiliations
Stanford University (US)
Corresponding author
Crabtree, Gerald R.
Venue
Nature Reviews Genetics
Published
2013-04-09
Volume
14
Issue
5
Pages
347-359
ISSN
  • 1471-0056 (ISSN-L)
  • 1471-0064
OpenAlex
W2060429763
Cited by
544
References
130
Citations by year
2026: 18 · 2025: 18 · 2024: 22 · 2023: 31 · 2022: 25 · 2021: 36 · 2020: 48 · 2019: 42 · 2018: 90 · 2017: 44 · 2016: 43 · 2015: 47 · 2014: 58 · 2013: 21
FWCI
6.93
Type
journal article
Language
en
Update notices
erratum (2013-05-09)
Open access
Locations
  • Nature Reviews Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • California Institute for Regenerative Medicine
  • California Institute of Regenerative Medicine
  • National Institutes of Health
  • National Cancer Institute (CA163915, R01CA163915)
  • National Institute of Neurological Disorders and Stroke (NS046789, R01NS046789, R37NS046789)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
chromatin regulation, neural development, neurodevelopmental disorders, mental illness, chromatin remodellers, histone-modifying enzymes, SWI/SNF complex, CHD8, HDAC4, EZH2, Polycomb, intellectual disability, cognitive impairment, cancer mutations
MeSH terms
Enhancer of Zeste Homolog 2 Protein, Animals, Chromatin, Cognition, DNA-Binding Proteins, Histone Deacetylases, Humans, Intellectual Disability, Mutation, Neurons, Nuclear Proteins, Repressor Proteins, Transcription Factors, Chromatin Assembly and Disassembly, Neurogenesis, Polycomb Repressive Complex 2

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