title: Yin-yang actions of histone methylation regulatory complexes in the brain.
abstract: Dysregulation of histone methylation has emerged as a major driver of neurodevelopmental disorders including intellectual disabilities and autism spectrum disorders. Histone methyl writer and eraser enzymes generally act within multisubunit complexes rather than in isolation. However, it remains largely elusive how such complexes cooperate to achieve the precise spatiotemporal gene expression in the developing brain. Histone H3K4 methylation (H3K4me) is a chromatin signature associated with active gene-regulatory elements. We review a body of literature that supports a model in which the RAI1-containing H3K4me writer complex counterbalances the LSD1-containing H3K4me eraser complex to ensure normal brain development. This model predicts H3K4me as the nexus of previously unrelated neurodevelopmental disorders.
authors.affiliation: Neuroscience Graduate Program, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Patricia Marie
authors.initials: PM
authors.lastname: Garay
authors.affiliation: The University of Michigan College of Literature, Science, & The Arts, Ann Arbor, MI 48109, USA.
authors.forename: Margarete Aryanka
authors.initials: MA
authors.lastname: Wallner
authors.affiliation: Neuroscience Graduate Program, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.|Department of Human Genetics, The University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Iwase
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism*; D025063:Chromosome Disorders / Q000235:genetics; D058674:Chromosome Duplication / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics; D056970:Co-Repressor Proteins / Q000235:genetics; D015870:Gene Expression; D006609:High Mobility Group Proteins / Q000235:genetics; D056466:Histone Demethylases / Q000235:genetics; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D058496:Smith-Magenis Syndrome / Q000235:genetics; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics
chemical_list: D056970:Co-Repressor Proteins; C408987:HMG20A protein, human; D006609:High Mobility Group Proteins; D006657:Histones; C497422:KMT2A protein, human; D009419:Nerve Tissue Proteins; C431552:RAI1 protein, human; C121019:RCOR1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D056466:Histone Demethylases; C495195:KDM1A protein, human; D011495:Histone-Lysine N-Methyltransferase
keywords: LSD1; PHF21A; RAI1; activity-dependent gene expression; autism spectrum disorders; chromatin regulatory complex; circadian gene expression; histone methylation; intellectual disability; neurodevelopmental disorders