Age-related difference of site-specific histone modifications in rat liver

Age-related difference of site-specific histone modifications in rat liver
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DOI:
10.1007/s10522-008-9176-0
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发表时间:
2009-08-01
期刊:
影响因子:
4.5
通讯作者:
Takahashi, Ryoya
Takahashi, Ryoya
中科院分区:
医学3区
文献类型:
--
作者:
Kawakami, Kyojiro;Nakamura, Akihiro;Takahashi, Ryoya

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衰老与转录、复制和DNA修复活动的减少有关,这可能导致细胞和组织功能的退化。随着年龄的增长,染色质结构的变化可能是功能下降的主要机制。染色质由DNA和组蛋白以及非组蛋白蛋白组成。虽然与年龄相关的DNA甲基化的变化是有据可查的,但关于衰老中位点特异性组蛋白修饰的信息很少。我们在这里研究了大鼠肝脏组蛋白的选定修饰的年龄相关变化,即,组蛋白H3 Lys9乙酰化(H3K9ac)、H3 Lys9甲基化(H3K9me)、H3 Ser10磷酸化(H3S10ph)和H3 Lys14乙酰化(H3K14ac)。H3K9ac随年龄增长而降低,H3S10ph随年龄增长而升高。鉴于有报道表明H3组蛋白乙酰化的减少和磷酸化的增加可以抑制基因活性,我们的研究结果表明,随着年龄的增长,染色质功能下降的机制是由于这种表观遗传变化。
Aging is associated with decrease in activities of the transcription, replication and DNA repair that can result in deterioration of cellular and tissue functions. Changes of chromatin structures with age are likely major underling mechanisms for the functional decline. Chromatin consists of DNA and histones as well as non-histone proteins. While age-associated change of DNA methylation is well documented, little information is available on site-specific histone modifications in aging. We studied here age-related change of selected modifications of rat liver histone, i.e., histone H3 Lys9 acetylation (H3K9ac), H3 Lys9 methylation (H3K9me), H3 Ser10 phosphorylation (H3S10ph) and H3 Lys14 acetylation (H3K14ac). H3K9ac was decreased and H3S10ph was increased with age significantly. In view of reports indicating that decrease in acetylation and increase in phosphorylation of H3 histones can suppress gene activity, our findings suggest that a mechanism of decreased chromatin functions with age is due to such epigenetic changes.