Epigenetic mechanisms underlying enhancer modulation of neuronal identity, neuronal activity and neurodegeneration

NEUROBIOLOGY OF DISEASE

卷:147

Review

Alcala-Vida, Rafael^1,2  Awada, Ali^1,2  Boutillier, Anne-Laurence^1,2  Merienne, Karine^1,2 

[1] Univ Strasbourg, LNCA, 12 Rue Goethe, F-67000 Strasbourg, France

[2] CNRS UMR 7364, 12 Rue Goethe, F-67000 Strasbourg, France

关键词: Epigenetic regulations;    Super enhancer;    Neuronal identity;    Neuronal activity;    Huntington's disease;    Alzheimer's disease;   

DOI  :  10.1016/j.nbd.2020.105155

来源: Elsevier

【 摘 要 】

Neurodegenerative diseases, including Huntington's disease (HD) and Alzheimer's disease (AD), are progressive conditions characterized by selective, disease-dependent loss of neuronal regions and/or subpopulations. Neuronal loss is preceded by a long period of neuronal dysfunction, during which glial cells also undergo major changes, including neuroinflammatory response. Those dramatic changes affecting both neuronal and glial cells associate with epigenetic and transcriptional dysregulations, characterized by defined cell-type-specific signatures. Notably, increasing studies support the view that altered regulation of transcriptional enhancers, which are distal regulatory regions of the genome capable of modulating the activity of promoters through chromatin looping, play a critical role in transcriptional dysregulation in HD and AD. We review current knowledge on enhancers in HD and AD, and highlight challenging issues to better decipher the epigenetic code of neurodegenerative diseases.