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Heterochromatin dysregulation in human diseases Hahn M; Dambacher S; Schotta GJ Appl Physiol (1985) 2010[Jul]; 109 (1): 232-42Heterochromatin is a repressive chromatin state that is characterized by densely packed DNA and low transcriptional activity. Heterochromatin-induced gene silencing is important for mediating developmental transitions, and in addition, it has more global functions in ensuring chromosome segregation and genomic integrity. Here we discuss how altered heterochromatic states can impair normal gene expression patterns, leading to the development of different diseases. Over the last years, therapeutic strategies that aim toward resetting the epigenetic state of dysregulated genes have been tested. However, due to the complexity of epigenetic gene regulation, the "first-generation drugs" that function globally by inhibiting epigenetic machineries might also introduce severe side effects. Thus detailed understanding of how repressive chromatin states are established and maintained at specific loci will be fundamental for the development of more selective epigenetic treatment strategies in the future.|*Epigenesis, Genetic[MESH]|Angelman Syndrome/genetics[MESH]|Animals[MESH]|Disease/*genetics[MESH]|Drosophila/genetics[MESH]|Female[MESH]|Friedreich Ataxia/genetics[MESH]|Gene Silencing[MESH]|Heterochromatin/*metabolism[MESH]|Humans[MESH]|Mice[MESH]|Muscular Dystrophy, Facioscapulohumeral/genetics[MESH]|Neoplasms/drug therapy/genetics[MESH]|Prader-Willi Syndrome/genetics[MESH] |
