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From neural development to cognition: unexpected roles for chromatin
Open accessAbstract
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 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.”
From Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015) · cites this paper as [110]
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“These ATP-dependent chromatin remodelling complexes consist of 15 subunits, including one of both ATPase core subunits SMARCA4 or SMARCA237.”
From A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP (2014) · cites this paper as [37]
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Metadata
- 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
- PMC
- PMC4010428
- 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
- green
- www.ncbi.nlm.nih.gov
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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