Genomic properties of variably methylated retrotransposons in mouse
Genomic properties of variably methylated retrotransposons in mouse
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小鼠可变甲基化逆转录转座子的基因组特性
DOI：
10.1101/2020.10.21.349217
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Elmer J
中科院分区：
文献类型：
--
作者：
Elmer J
背景转座因子（transposable elements，TEs）富含胞嘧啶甲基化，阻止了它们在基因组内的移动.我们以前确定了一个全基因组范围的候选人脑池内A颗粒（IAP）TEs在小鼠中表现出个体间差异，这种甲基化（VM-IAP）与基因组功能的影响。除了在所有组织中具有均匀甲基化的那些（组成型或cVM-IAP）之外，还存在tsVM-IAP;这两种类型都有可能调节基因切割。在其他TE的可变甲基化的筛选表明，这种现象主要限于IAP，这是最年轻和最活跃的内源性逆转录病毒。我们鉴定了在cVM-IAP内富集的序列，但确定这些不足以赋予表观遗传变异性。CTCF在VM-IAP处富集，结合与DNA甲基化负相关。我们发现动态的物理之间的相互作用cVM-IAP与低甲基化范围和其他基因组位点，表明VM-IAP具有潜在的远程regulation.ConclusionOur的研究结果表明，最近进化的基因序列之间的相互作用，CTCF结合，和DNA甲基化在年轻的TE可以导致个体间的变异与表型变异的转录结果的影响。
BackgroundTransposable elements (TEs) are enriched in cytosine methylation, preventing their mobility within the genome. We previously identified a genome-wide repertoire of candidate intracisternal A particle (IAP) TEs in mice that exhibit inter-individual variability in this methylation (VM-IAPs) with implications for genome function.ResultsHere we validate these metastable epialleles and discover a novel class that exhibit tissue specificity (tsVM-IAPs) in addition to those with uniform methylation in all tissues (constitutive- or cVM-IAPs); both types have the potential to regulate genes incis. Screening for variable methylation at other TEs shows that this phenomenon is largely limited to IAPs, which are amongst the youngest and most active endogenous retroviruses. We identify sequences enriched within cVM-IAPs, but determine that these are not sufficient to confer epigenetic variability. CTCF is enriched at VM-IAPs with binding inversely correlated with DNA methylation. We uncover dynamic physical interactions between cVM-IAPs with low methylation ranges and other genomic loci, suggesting that VM-IAPs have the potential for long-range regulation.ConclusionOur findings indicate that a recently evolved interplay between genetic sequence, CTCF binding, and DNA methylation at young TEs can result in inter-individual variability in transcriptional outcomes with implications for phenotypic variation.
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作者：
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影响因子：
3.9
作者：
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DOI：
--
发表时间：
2020
影响因子：
11.1
作者：
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通讯作者：
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