2. Academic Validation
  3. Disrupted intricacy of histone H3K4 methylation in neurodevelopmental disorders

Disrupted intricacy of histone H3K4 methylation in neurodevelopmental disorders

  • Epigenomics. 2015;7(3):503-19. doi: 10.2217/epi.15.1.
Christina N Vallianatos 1 2,  Shigeki Iwase 1
Affiliations

Affiliations

  • 1 Department of Human Genetics, University of Michigan, 5815 Medical Science II, Ann Arbor, MI 48109, USA.
  • 2 Predoctoral Training Program in Genetics, University of Michigan, 5815 Medical Science II, Ann Arbor, MI 48109, USA.
PMID: 26077434 DOI: 10.2217/epi.15.1
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.

Keywords

H3K4 methylation; autism spectrum disorders; brain development; chromatin; epigenetics; gene regulation; histone methylation; intellectual disability; schizophrenia.

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