Mechanisms of Disease: histone modifications in Huntington's disease

@article{SadriVakili2006MechanismsOD,
  title={Mechanisms of Disease: histone modifications in Huntington's disease},
  author={Ghazaleh Sadri-Vakili and Jang-Ho Cha},
  journal={Nature Clinical Practice Neurology},
  year={2006},
  volume={2},
  pages={330-338}
}
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a polyglutamine repeat expansion within the huntingtin protein. HD is characterized by problems with movement, cognition and behavioral functioning, and there is currently no effective treatment. Although multiple pathologic mechanisms have been proposed, the exact mechanism by which mutant huntingtin causes neuronal dysfunction is not known. Recent studies demonstrating altered messenger RNA expression… 
Epigenetic Mechanisms of Neurodegeneration in Huntington’s Disease
TLDR
How DNA methylation, post-translational modifications of histone, and noncoding RNA function are affected and involved in HD pathogenesis and the therapeutic effects of hist one deacetylase inhibitors and DNA binding drugs on epigenetic modifications and neuropathological sequelae in HD are discussed.
Inconsistencies in histone acetylation patterns among different HD model systems and HD post-mortem brains
Genome-Wide Histone Acetylation Is Altered in a Transgenic Mouse Model of Huntington's Disease
TLDR
It is demonstrated that histone H3 acetylation at lysine residues 9 and 14 and active gene expression are intimately tied in the rodent brain, and that this fundamental relationship remains unchanged in an HD mouse model despite genome-wide decreases in hist one H3acetylation.
Nucleolar dysfunction in Huntington's disease.
Chromosomal profiles of gene expression in Huntington's disease.
TLDR
Results show that transcription is indeed deregulated in large genomic regions in coordinated fashion, that transcription in these regions is associated with disease progression and that altered chromosomal clusters in the two tissues are remarkably similar.
Non-Cell Autonomous and Epigenetic Mechanisms of Huntington’s Disease
TLDR
This review addresses the conventional role of wild type HTT (wtHTT) and how mHTT protein disrupts the function of medium spiny neurons (MSNs).
Histones associated with downregulated genes are hypo-acetylated in Huntington's disease models.
TLDR
It is demonstrated that despite no change in overall acetylated histone levels, histone H3 is hypo-acetylated at promoters of downregulated genes in R6/2 mice, ST14a and STHdh cells, as demonstrated by in vivo chromatin immunoprecipitation.
Modulation of nucleosome dynamics in Huntington's disease.
TLDR
Improved nucleosomal dynamics were concurrent with a significant improvement in the behavioral and neuropathological phenotype observed in HD mice, showing the ability of anthracycline compounds to rebalance epigenetic histone modification and may provide the rationale for the design of human clinical trials in HD patients.
Transcriptional signatures in Huntington's disease
  • J. Cha
  • Biology
    Progress in Neurobiology
  • 2007
Molecular mechanisms and potential therapeutical targets in Huntington's disease.
TLDR
The data that describe the emergence of the ancient huntingtin gene and of the polyglutamine trait during the last 800 million years of evolution are reviewed and data indicating how the loss of these beneficial activities reduces the ability of these neurons to survive are summarized.
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