Chapter 9: Epigenetics and Down Syndrome

Abstract Down syndrome (DS), or trisomy 21, is the most common genetic intellectual disability. Although the triplication of chromosome 21 (HSA21) would theoretically lead to a 1.5-fold increase in gene transcription, transcript levels of many genes significantly deviate from this. Epigenetic mechanisms, including DNA methylation and posttranslational histone modifications, regulate gene expression, and mounting evidence indicates epigenetics to play an important role in learning, memory, and intellectual disabilities. Surprisingly, epigenetic marks have been hardly investigated in DS. Importantly, various overexpressed HSA21 proteins affect epigenetic mechanisms and DS individuals are thus likely to present epigenetic aberrations. Excitingly, epigenetic marks are reversible, offering a huge therapeutic potential to alleviate or cure certain genetic deficits. Epigenetic therapy is already used for cancer, and may also provide new avenues for cognition-enhancing treatment in DS. This chapter summarizes the current knowledge on epigenetics in DS and discusses the potential of epigenetic therapy to reverse dysregulated gene expression.