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[en] Recent studies suggested that Huntington's disease is due to aberrant interactions between mutant huntingtin protein, transcription factors and transcriptional co-activators resulting in widespread transcriptional dysregulation. Mutant huntingtin also interacts with histone acetyltransferases, consequently interfering with the acetylation and deacetylation states of histones. Because histone modifications and chromatin structure coordinate the expression of gene clusters, we have applied a novel mathematical approach, Chromowave, to analyse microarray datasets of brain tissue and whole blood to understand how genomic regions are altered by the effects of mutated huntingtin on chromatin structure. Results show that, in samples of caudate and whole blood from Huntington's disease patients, 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. These findings support the notion of a common genome-wide mechanism of disruption of RNA transcription in the brain and periphery of Huntington's disease patients.
Disciplines :
Neurology
Author, co-author :
Anderson, Alexander N; Hammersmith Hospital, London > MRC Clinical Sciences Centre
Roncaroli, Federico; Imperial College London > Department of Clinical Neuroscience
Hodges, Angela; Institute of Psychiatry, London, UK > MRC Centre for Neurodegeneration Research
Deprez, Manuel ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Turkheimer, Federico E; Hammersmith Hospital, London > MRC Clinical Sciences Centre
Language :
English
Title :
Chromosomal profiles of gene expression in Huntington's disease.
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