title: Nucleolar dysfunction in Huntington's disease.
abstract: Huntington's disease (HD) is a fatal genetic disorder characterized by triad clinical symptoms of chorea, emotional distress, and cognitive decline. Genetic mutation in HD is identified by an expansion of CAG repeats coding for glutamine (Q) in exon 1 of the huntingtin (htt) gene. The exact mechanism on how mutant htt leads to the selective loss of medium spiny neurons (MSNs) in the striatum is still unknown. Recent studies suggest that nucleolar stress and dysfunction are linked to the pathogenesis of HD. Alterations of the nucleolar activity and integrity contribute to deregulation of ribosomal DNA (rDNA) transcription in HD pathogenesis. Furthermore, epigenetic modifications in the nucleolus are associated with neuronal damage in HD. In this review, we discuss about how post-translational modifications of upstream binding factor (UBF) are affected by histone acetyltransferase and histone methyltransferase and involved in the transcriptional regulation of rDNA in HD. The understanding of epigenetic modulation of UBF-dependent rDNA transcription in the nucleolus may lead to the identification of novel pathological markers and new therapeutic targets to treat HD. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease.
authors.affiliation: VA Boston Healthcare System, Boston, MA 02130, USA; Boston University, Alzheimer's Disease Center, Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Junghee
authors.initials: J
authors.lastname: Lee
authors.affiliation: WCU Neurocytomics Group, Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 110-799, South Korea.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Hwang
authors.affiliation: Boston University, Alzheimer's Disease Center, Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Hyun
authors.initials: H
authors.lastname: Ryu
authors.affiliation: VA Boston Healthcare System, Boston, MA 02130, USA; Boston University, Alzheimer's Disease Center, Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Neil W
authors.initials: NW
authors.lastname: Kowall
authors.affiliation: VA Boston Healthcare System, Boston, MA 02130, USA; Boston University, Alzheimer's Disease Center, Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA; Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology, Seoul, South Korea. Electronic address: hoonryu@bu.edu.
authors.forename: Hoon
authors.initials: H
authors.lastname: Ryu
mesh_terms: D000107:Acetylation; D002466:Cell Nucleolus / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D044127:Epigenesis, Genetic / Q000235:genetics*; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics* / Q000473:pathology; D008745:Methylation; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D035463:Pol1 Transcription Initiation Complex Proteins / Q000235:genetics / Q000378:metabolism*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D035463:Pol1 Transcription Initiation Complex Proteins; C063844:transcription factor UBF
keywords: Acetylation and methylation; Epigenetics; Huntington's disease; Nucleolus; Upstream binding factor (UBF); rDNA transcription