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基于逆转录转座子的哺乳动物表观基因组分析:胚胎干细胞、体细胞和癌细胞中IAP长末端重复序列的DNA甲基化

Retrotransposon-based profiling of mammalian epigenomes: DNA methylation of IAP LTRs in embryonic stem, somatic and cancer cells.

作者信息

Bakshi Arundhati, Kim Joomyeong

机构信息

Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.

Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.

出版信息

Genomics. 2014 Dec;104(6 Pt B):538-44. doi: 10.1016/j.ygeno.2014.09.009. Epub 2014 Sep 29.

Abstract

In the current study, we have used HT-TREBS to individually analyze the DNA methylation pattern of 4799 IAP LTR retrotransposons in embryonic stem, somatic and Neuro2A cells. According to the results, half of the loci within this family show constant methylation patterns between the three cell types whereas the remaining half display variable levels of methylation. About half of the variably methylated IAP LTRs tend to be hypomethylated in ES cells, and nearly all in this group are hypomethylated in Neuro2A cells. The observed hypomethylation in both cell types occur in a non-uniform, locus-specific manner and to various degrees of severity, with some of them being easily detectible by COBRA. Overall, this study demonstrates the feasibility of HT-TREBS to study DNA methylation changes at retrotransposons in a locus-specific manner in multiple cell types and further suggests the potential utility of this technique in developing epigenetic biomarkers for tracking disease progression.

摘要

在当前研究中,我们使用了HT-TREBS分别分析胚胎干细胞、体细胞和Neuro2A细胞中4799个IAP LTR逆转座子的DNA甲基化模式。根据结果,该家族中一半的位点在三种细胞类型之间呈现出恒定的甲基化模式,而其余一半则表现出可变的甲基化水平。约一半可变甲基化的IAP LTR在胚胎干细胞中倾向于低甲基化,并且该组中几乎所有的在Neuro2A细胞中都是低甲基化的。在这两种细胞类型中观察到的低甲基化以非均匀、位点特异性的方式发生,且程度各异,其中一些可以通过COBRA轻松检测到。总体而言,本研究证明了HT-TREBS以位点特异性方式研究多种细胞类型中逆转座子DNA甲基化变化的可行性,并进一步表明了该技术在开发用于追踪疾病进展的表观遗传生物标志物方面的潜在用途。

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