Age-associated activation of epigenetically repressed genes in the mouse.
Age-associated activation of epigenetically repressed genes in the mouse.
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DOI：
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发表时间：
2003-12
期刊：
影响因子：
3.3
通讯作者：
P. Bennett-Baker;J. Wilkowski;D. Burke
中科院分区：
文献类型：
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作者：
P. Bennett-Baker;J. Wilkowski;D. Burke
基因表达的表观遗传控制是分化的哺乳动物细胞类型的一致特征。表观遗传表达模式是有丝分裂遗传的，并在成体细胞中稳定维持。然而，与体细胞DNA突变不同，人们对正常成年生活中表观遗传变化或表观突变的发生知之甚少。我们已经监测了年龄相关的维护两个表观遗传系统-X失活和基因组印记-分别使用基因Atp 7a和Igf 2。在2至24月龄的小鼠中对来自非活性和活性等位基因的RNA转录物进行定量测量。对于这两个基因，老年动物队列显示从沉默的等位基因表达的转录本的可重复增加。X染色体沉默的丢失显示队列平均增加高达2.2%，而印记基因激活增加高达6.7%。结果支持这一假设，即基因抑制的表观遗传丢失发生在正常组织中，可能是哺乳动物衰老过程中观察到的进行性生理功能障碍的一个促成因素。从数量上看，表观遗传控制的丧失可能比之前确定的体细胞DNA突变大一到两个数量级。
Epigenetic control of gene expression is a consistent feature of differentiated mammalian cell types. Epigenetic expression patterns are mitotically heritable and are stably maintained in adult cells. However, unlike somatic DNA mutation, little is known about the occurrence of epigenetic change, or epimutation, during normal adult life. We have monitored the age-associated maintenance of two epigenetic systems--X inactivation and genomic imprinting--using the genes Atp7a and Igf2, respectively. Quantitative measurements of RNA transcripts from the inactive and active alleles were performed in mice from 2 to 24 months of age. For both genes, older animal cohorts showed reproducible increases in transcripts expressed from the silenced alleles. Loss of X chromosome silencing showed cohort mean increases of up to 2.2%, while imprinted-gene activation increased up to 6.7%. The results support the hypothesis that epigenetic loss of gene repression occurs in normal tissues and may be a contributing factor in progressive physiological dysfunction seen during mammalian aging. Quantitatively, the loss of epigenetic control may be one to two orders of magnitude greater than previously determined somatic DNA mutation.