Abstract
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.
Financial & competing interests disclosure
CN Vallianatos is supported, in part, by an NIH training grant (T32GM07544), ‘Michigan Predoctoral Training in Genetics’, and the Farrehi research fund. S Iwase is supported by Cooley’s Anemia Foundation and the University of Michigan Medical School. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.