Epigenetics and Triplet-Repeat Neurological Diseases.
Epigenetics and Triplet-Repeat Neurological Diseases.
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表观遗传学和三胞胎重复神经疾病。
DOI：
10.3389/fneur.2015.00262
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发表时间：
2015
影响因子：
3.4
通讯作者：
Festenstein R
中科院分区：
文献类型：
--
作者：
Nageshwaran S;Festenstein R
在描述重复 DNA 区域的功能意义后，“垃圾 DNA”一词已被重新考虑。 DNA 重复通常与着丝粒和端粒相关，几乎在所有生物体的整个基因组中都存在。重复区域经常异染色质化，导致内在基因和附近基因的沉默。然而，这并不是一个统一的规则，已知有几种基因需要这样的环境才能进行转录。重复区域经常以二核苷酸、三核苷酸和四核苷酸重复形式存在。 1991 年，在脊髓和延髓性肌萎缩症（肯尼迪病）和精神发育迟滞的脆性 X 综合征 (FRAXA) 中发现异常三核苷酸重复后，重复区域与疾病之间的关联得到了强调。在这篇综述中，我们简要概述了表观遗传机制，然后重点关注由 DNA 三联体重复扩增引起的几种疾病，这些疾病表现出 多样的表观遗传效应。显然，新兴的表观遗传学领域已经为这组基本上无法治愈的疾病创造了新的潜在治疗途径。
The term “junk DNA” has been reconsidered following the delineation of the functional significance of repetitive DNA regions. Typically associated with centromeres and telomeres, DNA repeats are found in nearly all organisms throughout their genomes. Repetitive regions are frequently heterochromatinized resulting in silencing of intrinsic and nearby genes. However, this is not a uniform rule, with several genes known to require such an environment to permit transcription. Repetitive regions frequently exist as dinucleotide, trinucleotide, and tetranucleotide repeats. The association between repetitive regions and disease was emphasized following the discovery of abnormal trinucleotide repeats underlying spinal and bulbar muscular atrophy (Kennedy’s disease) and fragile X syndrome of mental retardation (FRAXA) in 1991. In this review, we provide a brief overview of epigenetic mechanisms and then focus on several diseases caused by DNA triplet-repeat expansions, which exhibit diverse epigenetic effects. It is clear that the emerging field of epigenetics is already generating novel potential therapeutic avenues for this group of largely incurable diseases.