Instability and chromatin structure of expanded trinucleotide repeats.

Instability and chromatin structure of expanded trinucleotide repeats.
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DOI:
10.1016/j.tig.2009.04.007
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发表时间:
2009-07
期刊:
影响因子:
11.4
通讯作者:
Wilson, John H.
Wilson, John H.
中科院分区:
生物学1区
文献类型:
--
作者:
Dion, Vincent;Wilson, John H.

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三核苷酸重复扩增是至少17种神经系统疾病的基础。在受影响的个体中,扩展位点的特征是染色质结构和重复束长度的急剧变化。有趣的是,最近的研究表明,一些染色质修饰剂,包括组蛋白乙酰转移酶、DNA甲基转移酶和转录因子CTCF可以调节重复不稳定性。在这里,我们提出扩展重复序列不寻常的染色质结构直接影响它们的不稳定性。我们讨论了这可能发生的几种潜在模型,包括DNA修复依赖的表观遗传重编程在增加重复不稳定性中的作用,以及表观遗传标记改变义和反义转录的能力,从而影响重复不稳定性。
Trinucleotide repeat expansion underlies at least 17 neurologic diseases. In affected individuals, the expanded locus is characterized by dramatic changes in chromatin structure and in repeat tract length. Interestingly, recent studies show that several chromatin modifiers, including a histone acetyltransferase, a DNA methyltransferase, and the transcription factor CTCF can modulate repeat instability. Here, we propose that the unusual chromatin structure of expanded repeats directly impacts their instability. We discuss several potential models for how this might occur, including a role for DNA repair-dependent epigenetic reprogramming in increasing repeat instability, and the capacity of epigenetic marks to alter sense and antisense transcription, thereby affecting repeat instability.
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