Histone acetylation, acetyltransferases, and ataxia--alteration of histone acetylation and chromatin dynamics is implicated in the pathogenesis of polyglutamine-expansion disorders.

摘要: Eukaryotic chromosomal DNA is packaged into nucleosomes to form a dynamic structure known as chromatin. The compaction of within chromatin poses unique hindrance with regards the accessibility enzymes involved in replication, transcriptional regulation, and repair. physical physiological activity are regulated through diverse set posttranslational modifications, histone exchange, structural remodeling. Of covalent acetylation lysine residues proteins by acetyltransferase enzymes, such GCN5, one most prevalent important steps regulation function. Alteration can easily result dysregulation gene transcription ultimately onset disease state. Many factors contain polyglutamine regions their primary sequence. Mutations resulting elongation these tracts associated family expansion disorders. Spinocerebellar ataxia type 7 (SCA7) nine diseases that grouped this caused ataxin-7 protein, which component GCN5-containing human SAGA complex. Mutation manner has been shown disrupt integrity complex aberrant patterns at promoters genes normal function tissues affected disease. specific aspects molecular pathology not currently understood; however, studies carried out laboratory systems ranging from budding yeast Saccharomyces cerevisiae transgenic mouse models cultured cells poised allow for elucidation mechanisms subsequent therapeutic approaches.