Autism-like syndrome is induced by pharmacological suppression of BET proteins in young mice

作者:Sullivan Josefa M; Badimon Ana; Schaefer Uwe; Ayata Pinar; Gray James; Chung Chun wa; von Schimmelmann Melanie; Zhang Fan; Garton Neil; Smithers Nicholas; Lewis Huw; Tarakhovsky Alexander; Prinjha Rab K; Schaefer Anne
来源:Journal of Experimental Medicine, 2015, 212(11): 1771-1781.
DOI:10.1084/jem.20151271

摘要

Studies investigating the causes of autism spectrum disorder (ASD) point to genetic, as well as epigenetic, mechanisms of the disease. Identification of epigenetic processes that contribute to ASD development and progression is of major importance and may lead to the development of novel therapeutic strategies. Here, we identify the bromodomain and extraterminal domain-containing proteins (BETs) as epigenetic regulators of genes involved in ASD-like behaviors in mice. We found that the pharmacological suppression of BET proteins in the brain of young mice, by the novel, highly specific, brain-permeable inhibitor I-BET858 leads to selective suppression of neuronal gene expression followed by the development of an autism-like syndrome. Many of the I-BET858-affected genes have been linked to ASD in humans, thus suggesting the key role of the BET-controlled gene network in the disorder. Our studies suggest that environmental factors controlling BET proteins or their target genes may contribute to the epigenetic mechanism of ASD.

  • 出版日期2015-10-19