Thomson Sarah B, Leavitt Blair R
Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, and BC Children's Hospital, Vancouver, BC, Canada.
Department of Medicine, Centre for Brain Health, and Division of Neurology, University of British Columbia Hospital, Vancouver, BC, Canada.
J Huntingtons Dis. 2018;7(4):289-296. doi: 10.3233/JHD-180331.
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG trinucleotide expansion in the HTT gene, which encodes for an abnormal polyglutamine tract in the huntingtin protein (HTT). This review examines the known mechanisms of HTT gene regulation. We discuss HTT expression patterns, features of the HTT promoter, regulatory regions of the HTT promoter with functional significance, and HTT regulators located outside of the proximal promoter region. The factors that influence HTT expression in the brain and the mechanisms of HTT transcriptional regulation are currently poorly understood, despite continuing research. Expanding knowledge of HTT regulation will inform future studies investigating HTT function. Improving understanding of HTT expression and control may also uncover novel therapeutic approaches for HD through the development of methods to modulate mHTT levels.
亨廷顿舞蹈症(HD)是一种常染色体显性神经退行性疾病,由HTT基因中的CAG三核苷酸重复扩增引起,该基因编码亨廷顿蛋白(HTT)中的异常多聚谷氨酰胺序列。本综述探讨了HTT基因调控的已知机制。我们讨论了HTT的表达模式、HTT启动子的特征、具有功能意义的HTT启动子调控区域以及位于近端启动子区域之外的HTT调节因子。尽管研究仍在继续,但目前对影响大脑中HTT表达的因素以及HTT转录调控机制的了解仍很有限。对HTT调控的深入了解将为未来研究HTT功能提供参考。通过开发调节突变型HTT水平的方法,更好地理解HTT的表达和调控也可能揭示HD的新型治疗方法。