Journal
EPIGENOMICS
Volume 7, Issue 3, Pages 503-518Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/epi.15.1
Keywords
autism spectrum disorders; brain development; chromatin; epigenetics; gene regulation; H3K4 methylation; histone methylation; intellectual disability; schizophrenia
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Funding
- NIH [T32GM07544]
- Farrehi research fund
- Cooley's Anemia Foundation
- University of Michigan Medical School
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [T32HD079342] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM007544] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS089896] Funding Source: NIH RePORTER
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Methylation of histone H3 lysine 4 (H3K4me) is an intricately regulated posttranslational modification, which is broadly associated with enhancers and promoters of actively transcribed genomic loci. Recent advances in next-generation sequencing have identified a number of H3K4me regulators mutated in neurodevelopmental disorders including intellectual disabilities, autism spectrum disorders, and schizophrenia. Here, we aim to summarize the molecular function of H3K4me-regulating enzymes in brain development and function. We describe four H3K4me methyltransferases (KMT2A, KMT2C, KMT2D, KMT2F), four demethylases (KDM1A, KDM5A, KDM5B, KDM5C), and two reader proteins (PHF21A, PHF8) mutated in neurodevelopmental disorders. Understanding the role of these chromatin regulators in the development and maintenance of neural connections will advance therapeutic opportunities for prevention and treatment of these lifelong neurodevelopmental disorders.
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