Stage-specific H3K9me3 occupancy ensures retrotransposon silencing in human pre-implantation embryos
Ruimin XuSen LiQiu WuChong LiMan‐Xi JiangЛэй ГуоChen MoLingyue YangXin DongHong WangChenfei WangXiaoyu LiuXiang‐Hong OuShaorong Gao
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H3K4me3
Inner cell mass
Retrotransposon
Epigenome
Epigenome profiling has led to the paradigm that promoters of active genes are decorated with H3K4me3 and H3K9ac marks. To explore the epigenome of Plasmodium falciparum asexual stages, we performed MS analysis of histone modifications and found a general preponderance of H3/H4 acetylation and H3K4me3. ChIP-on-chip profiling of H3, H3K4me3, H3K9me3, and H3K9ac from asynchronous parasites revealed an extensively euchromatic epigenome with heterochromatin restricted to variant surface antigen gene families (VSA) and a number of genes hitherto unlinked to VSA. Remarkably, the vast majority of the genome shows an unexpected pattern of enrichment of H3K4me3 and H3K9ac. Analysis of synchronized parasites revealed significant developmental stage specificity of the epigenome. In rings, H3K4me3 and H3K9ac are homogenous across the genes marking active and inactive genes equally, whereas in schizonts, they are enriched at the 5' end of active genes. This study reveals an unforeseen and unique plasticity in the use of the epigenetic marks and implies the presence of distinct epigenetic pathways in gene silencing/activation throughout the erythrocytic cycle.
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Euchromatin
Heterochromatin protein 1
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Long interspersed elements 1 (LINE-1 or L1) are currently the only active form of autonomous retrotransposons that exist in the human genome. The 6 kb L1 element encodes its own proteins to mediate retrotransposition without the aid of components from other retrotransposons.
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ABSTRACT Transposable elements have had a profound impact on the structure and function of mammalian genomes. The retrotransposon Long INterspersed Element-1 (LINE-1 or L1), by virtue of its replicative mobilization mechanism, comprises ∼17% of the human genome. Although the vast majority of human LINE-1 sequences are inactive molecular fossils, an estimated 80–100 copies per individual retain the ability to mobilize by a process termed retrotransposition. Indeed, LINE-1 is the only active, autonomous retrotransposon in humans and its retrotransposition continues to generate both intra-individual and inter-individual genetic diversity. Here, we briefly review the types of transposable elements that reside in mammalian genomes. We will focus our discussion on LINE-1 retrotransposons and the non-autonomous Short INterspersed Elements (SINEs) that rely on the proteins encoded by LINE-1 for their mobilization. We review cases where LINE-1-mediated retrotransposition events have resulted in genetic disease and discuss how the characterization of these mutagenic insertions led to the identification of retrotransposition-competent LINE-1s in the human and mouse genomes. We then discuss how the integration of molecular genetic, biochemical, and modern genomic technologies have yielded insight into the mechanism of LINE-1 retrotransposition, the impact of LINE-1-mediated retrotransposition events on mammalian genomes, and the host cellular mechanisms that protect the genome from unabated LINE-1-mediated retrotransposition events. Throughout this review, we highlight unanswered questions in LINE-1 biology that provide exciting opportunities for future research. Clearly, much has been learned about LINE-1 and SINE biology since the publication of Mobile DNA II thirteen years ago. Future studies should continue to yield exciting discoveries about how these retrotransposons contribute to genetic diversity in mammalian genomes.
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Abstract Individual analysis of the epigenome of preimplantation embryos is useful for characterizing each embryo and for investigating the effects of environmental factors on their epigenome. However, it is difficult to analyze genome-wide epigenetic modifications, especially histone modifications, in a large number of single embryos due to the small number of cells and the complexity of the analysis methods. To solve this problem, we further modified the CUT&Tag method, which can analyze histone modifications in a small number of cells, such that the embryo is handled as a cell mass in the reaction solutions in the absence of the solid-phase magnetic beads that are used for antibody and enzyme reactions in the original method (NON-TiE-UP CUT&Tag; NTU-CAT). By using bovine blastocysts as a model, we showed that genome-wide profiles of representative histone modifications, H3K4me3 and H3K27me3, could be obtained by NTU-CAT that are in overall agreement with the conventional chromatin immunoprecipitation-sequencing (ChIP-seq) method, even from single embryos. However, this new approach has limitations that require attention, including false positive peaks and lower resolution for broad modifications. Despite these limitations, we conclude that NTU-CAT is a promising replacement for ChIP-seq with the great advantage of being able to analyze individual embryos.
Epigenome
H3K4me3
Chromatin immunoprecipitation
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Retrotransposons with high copy numbers and extensive sequence heterogeneity are widely distributed in higher plants. Retrotransposons can be divided into three major classes according to their structure organization and the amino acid sequences of the encoded reverse transcriptase. They are Ty1 copia like retrotransposons, Ty3 gypsy like retrotransposons, and LINE (long interspersed nuclear elements) like retrotransposons. Retrotransposons have been found in the flanking regions of normal plant genes. These elements may provide regulatory sequences for gene expression and may be involved in gene duplication during evolution. So far, transcriptionally active retrotransposons are only identified in the root of tobacco under normal developmental and growth conditions. Most of the retroelements in plants appear to be “genomic parasites. But they contribute greatly to the genetic diversity and genome size variability of plants. Some silent retrotransposons in plant genomes only possess the capability to transpose under certain circumstances, such as tissue culture or stimulation by microbial elicitors. The expression of these retrotransposons produces mutant progeny which may be useful for crop improvement and natural selection. Recently, active retrotransposons of tobacco were introduced into a few heterogeneous plant species. These elements transposed in the genome of new hosts which reveals the possibility of using retroelements to study plant gene functions.
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Interspersed repeat
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长终端的 Ty1-copia 和 Ty3 吉普赛人组的基因重复的反向的 transcriptase (RT )(LTR ) 的保存领域 retrotransposons 从 Malus 被孤立国内用退化 oligonucleotide 教材的一个染色体。顺序分析证明 45% Ty1-copia 和 63%Ty3 吉普赛人 RT 序列包含了破坏读的框架的早熟的站鳕鱼 ons 或 indels。在 Ty1-copia 和 Ty3 吉普赛人组 retrotransposons 的 RT 序列之中的高异质被观察,但是在苹果染色体的 Ty3 吉普赛人组 retrotransposons 不比 Ty1-copia 元素异构。Retrotransposon 拷贝数字被点污点杂交为 Ty1-copia 估计(∼5 000 ) 并且 Ty3 吉普赛人(∼26 000 ) 。LTR retrotransposons 的二种类型的所有元素包括约 38% M。国内一个染色体,与更高的 Ty3 吉普赛人组贡献(33.5%) 比 Ty1-copia (4.6%) 。抄写没被反向的抄写聚合酶链反应在 vitro 或在在与高集中 benzylaminopurine 补充的媒介上有教养的叶将生物的活组织移植于培养基中培养在植物的叶子为 Ty1-copia 或 Ty3 吉普赛人 retrotransposons 检测。这研究在苹果染色体在在 Ty1-copia 和 Ty3 吉普赛人 retrotransposons 之间的异质和拷贝数字揭示差别。Ty1-copia retrotransposon 比 Ty3 吉普赛人 retrotransposon 有更高的异质,但是后者让一个更高的拷贝数,它暗示 Ty3 吉普赛人 retrotransposons 可以在苹果染色体进化起一个更重要的作用。
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DNA transposons are the mobile elements that move by a "cut and paste" mechanism (1 , 2). In contrast, retrotransposons encode reverse transcriptase, and move by a "copy and paste" mechanism. The process of retrotransposon insertion into genomic locations involves an RNA intermediate. Retrotransposons can be classified into long terminal repeat (LTR) and non-LTR retrotransposons. LTR retrotransposons have LTRs at both ends and resemble retroviruses in both structure and integration mechanisms. Non-LTR retrotransposons comprise two subtypes, long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs). Non-LTR retrotransposons are in general 4 to 7 kb long and do not carry LTRs, and their retrotransposition mechanism is different from that of LTR retrotransposons. SINEs are nonautonomous retrotransposons of 100 to 500 bp that do not encode proteins. It has been proposed that the proteins encoded by LINEs are the source of the enzymatic retrotransposition machinery of SINEs (3 , 4 , 5).
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Abstract Individual analysis of the epigenome of preimplantation embryos is useful for characterizing each embryo and for investigating the effects of environmental factors on their epigenome. However, it is difficult to analyze genome-wide epigenetic modifications, especially histone modifications, in a large number of single embryos due to the small number of cells and the complexity of the analysis methods. To solve this problem, we further modified the CUT&Tag method, which can analyze histone modifications in a small number of cells, such that the embryo is handled as a cell mass in the reaction solutions in the absence of the solid-phase magnetic beads that are used for antibody and enzyme reactions in the conventional method (NON-TiE-UP CUT&Tag; NTU-CAT). By using bovine blastocysts as a model, we showed that genome-wide profiles of representative histone modifications, H3K4me3 and H3K27me3, could be obtained by NTU-CAT that are in overall agreement with the conventional chromatin immunoprecipitation-sequencing (ChIP-seq) method, even from single embryos. However, this new approach has limitations that require attention, including false positive and negative peaks and lower resolution for broad modifications. Despite these limitations, we consider NTU-CAT a promising replacement for ChIP-seq with the great advantage of being able to analyze individual embryos.
Epigenome
H3K4me3
Chromatin immunoprecipitation
Profiling (computer programming)
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Retrotransposons, a subclass of mobile genetic elements, have been discovered in many organisms. In this study, we identified a plant-specific retrotransposon (Sukkula) in the human genome (24 different DNA samples) by using retrotransposon-based molecular marker technique: inter-retrotransposon amplified polymorphism. There were five different groups related to the ages of the subjects. The polymorphism ratios were 8%–100% among all samples, 10%–91% among females (12 subjects) and 13%–100% among males (12 subjects). Moreover, we also observed 8%–91% polymorphism ratios when comparing males to females. To the best of our knowledge, this is one of the first reports on plant-specific retrotransposons in the human genome. The obtained findings are expected to contribute to broadening the knowledge about plant retrotransposons in the human genome and their role in human genome evolution.
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