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RepEnTools: an automated repeat enrichment analysis package for ChIP-seq data reveals hUHRF1 Tandem-Tudor domain enrichment in young repeats RepEnTools:用于 ChIP-seq 数据的自动重复富集分析软件包,揭示了 hUHRF1 Tandem-Tudor 结构域在年轻重复序列中的富集情况
IF 4.9 2区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-04-03 DOI: 10.1186/s13100-024-00315-y
Michel Choudalakis, Pavel Bashtrykov, Albert Jeltsch
Repeat elements (REs) play important roles for cell function in health and disease. However, RE enrichment analysis in short-read high-throughput sequencing (HTS) data, such as ChIP-seq, is a challenging task. Here, we present RepEnTools, a software package for genome-wide RE enrichment analysis of ChIP-seq and similar chromatin pulldown experiments. Our analysis package bundles together various software with carefully chosen and validated settings to provide a complete solution for RE analysis, starting from raw input files to tabular and graphical outputs. RepEnTools implementations are easily accessible even with minimal IT skills (Galaxy/UNIX). To demonstrate the performance of RepEnTools, we analysed chromatin pulldown data by the human UHRF1 TTD protein domain and discovered enrichment of TTD binding on young primate and hominid specific polymorphic repeats (SVA, L1PA1/L1HS) overlapping known enhancers and decorated with H3K4me1-K9me2/3 modifications. We corroborated these new bioinformatic findings with experimental data by qPCR assays using newly developed primate and hominid specific qPCR assays which complement similar research tools. Finally, we analysed mouse UHRF1 ChIP-seq data with RepEnTools and showed that the endogenous mUHRF1 protein colocalizes with H3K4me1-H3K9me3 on promoters of REs which were silenced by UHRF1. These new data suggest a functional role for UHRF1 in silencing of REs that is mediated by TTD binding to the H3K4me1-K9me3 double mark and conserved in two mammalian species. RepEnTools improves the previously available programmes for RE enrichment analysis in chromatin pulldown studies by leveraging new tools, enhancing accessibility and adding some key functions. RepEnTools can analyse RE enrichment rapidly, efficiently, and accurately, providing the community with an up-to-date, reliable and accessible tool for this important type of analysis.
重复元件(REs)对健康和疾病中的细胞功能起着重要作用。然而,在短读数高通量测序(HTS)数据(如 ChIP-seq)中进行 RE 富集分析是一项具有挑战性的任务。在这里,我们介绍 RepEnTools,这是一个用于 ChIP-seq 和类似染色质下拉实验的全基因组 RE 富集分析的软件包。我们的分析软件包将各种软件与精心选择和验证的设置捆绑在一起,提供了从原始输入文件到表格和图形输出的 RE 分析完整解决方案。即使只有最低限度的 IT 技能(Galaxy/UNIX),也能轻松实现 RepEnTools。为了证明 RepEnTools 的性能,我们分析了人类 UHRF1 TTD 蛋白结构域的染色质 pulldown 数据,发现在与已知增强子重叠并有 H3K4me1-K9me2/3 修饰的幼年灵长类和类人特异多态重复序列(SVA、L1PA1/L1HS)上 TTD 结合富集。我们利用新开发的灵长类和类人猿特异性 qPCR 检测方法,通过 qPCR 检测实验数据证实了这些新的生物信息学发现,这些检测方法是对类似研究工具的补充。最后,我们利用 RepEnTools 分析了小鼠 UHRF1 ChIP-seq 数据,结果表明内源性 mUHRF1 蛋白与被 UHRF1 沉默的 RE 启动子上的 H3K4me1-H3K9me3 共同定位。这些新数据表明,UHRF1在REs沉默中的功能作用是通过TTD与H3K4me1-K3K9me3双标记的结合来介导的,并且在两个哺乳动物物种中是保守的。RepEnTools 利用新工具,提高了可访问性,并增加了一些关键功能,从而改进了染色质 pulldown 研究中先前可用的 RE 富集分析程序。RepEnTools 可以快速、高效、准确地分析 RE 富集,为这一重要类型的分析提供了最新、可靠、易用的工具。
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引用次数: 0
Orthoptera-TElib: a library of Orthoptera transposable elements for TE annotation. Orthoptera-TElib:用于 TE 注释的 Orthoptera 转座元件库。
IF 4.9 2区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-03-15 DOI: 10.1186/s13100-024-00316-x
Xuanzeng Liu, Lina Zhao, Muhammad Majid, Yuan Huang

Transposable elements (TEs) are a major component of eukaryotic genomes and are present in almost all eukaryotic organisms. TEs are highly dynamic between and within species, which significantly affects the general applicability of the TE databases. Orthoptera is the only known group in the class Insecta with a significantly enlarged genome (0.93-21.48 Gb). When analyzing the large genome using the existing TE public database, the efficiency of TE annotation is not satisfactory. To address this limitation, it becomes imperative to continually update the available TE resource library and the need for an Orthoptera-specific library as more insect genomes are publicly available. Here, we used the complete genome data of 12 Orthoptera species to de novo annotate TEs, then manually re-annotate the unclassified TEs to construct a non-redundant Orthoptera-specific TE library: Orthoptera-TElib. Orthoptera-TElib contains 24,021 TE entries including the re-annotated results of 13,964 unknown TEs. The naming of TE entries in Orthoptera-TElib adopts the same naming as RepeatMasker and Dfam and is encoded as the three-level form of "level1/level2-level3". Orthoptera-TElib can be directly used as an input reference database and is compatible with mainstream repetitive sequence analysis software such as RepeatMasker and dnaPipeTE. When analyzing TEs of Orthoptera species, Orthoptera-TElib performs better TE annotation as compared to Dfam and Repbase regardless of using low-coverage sequencing or genome assembly data. The most improved TE annotation result is Angaracris rhodopa, which has increased from 7.89% of the genome to 53.28%. Finally, Orthoptera-TElib is stored in Sqlite3 for the convenience of data updates and user access.

可转座元件(TE)是真核生物基因组的主要组成部分,几乎存在于所有真核生物中。在物种之间和物种内部,可转座元具有高度的动态性,这极大地影响了可转座元数据库的普遍适用性。直翅目是昆虫类中唯一一个已知基因组显著增大(0.93-21.48 Gb)的类群。使用现有的 TE 公共数据库分析庞大的基因组时,TE 注释的效率并不理想。为了解决这一局限性,当务之急是不断更新现有的 TE 资源库,并且随着更多昆虫基因组的公开,有必要建立一个直翅目昆虫特异性资源库。在这里,我们利用 12 个直翅目物种的全基因组数据对 TE 进行了全新注释,然后对未分类的 TE 进行了人工再注释,从而构建了一个非冗余的直翅目特异性 TE 库:Orthoptera-TElib。Orthoptera-TElib 包含 24,021 个 TE 条目,其中包括 13,964 个未知 TE 的重新标注结果。Orthoptera-TElib 中 TE 条目的命名采用了与 RepeatMasker 和 Dfam 相同的命名方式,并以 "level1/level2-level3 "的三级形式编码。Orthoptera-TElib 可直接用作输入参考数据库,与 RepeatMasker 和 dnaPipeTE 等主流重复序列分析软件兼容。在分析直翅目物种的 TE 时,无论使用低覆盖率测序数据还是基因组组装数据,Orthoptera-TElib 的 TE 注释效果都优于 Dfam 和 Repbase。TE注释结果改善最大的物种是蝼蛄(Angaracris rhodopa),从占基因组的 7.89% 增加到 53.28%。最后,Orthoptera-TElib 存储在 Sqlite3 中,以方便数据更新和用户访问。
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引用次数: 0
The role of Smarcad1 in retroviral repression in mouse embryonic stem cells Smarcad1 在小鼠胚胎干细胞逆转录病毒抑制中的作用
IF 4.9 2区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-03-11 DOI: 10.1186/s13100-024-00314-z
Igor Bren, Ayellet Tal, Carmit Strauss, Sharon Schlesinger
Moloney murine leukemia virus (MLV) replication is suppressed in mouse embryonic stem cells (ESCs) by the Trim28-SETDB1 complex. The chromatin remodeler Smarcad1 interacts with Trim28 and was suggested to allow the deposition of the histone variant H3.3. However, the role of Trim28, H3.3, and Smarcad1 in MLV repression in ESCs still needs to be fully understood. In this study, we used MLV to explore the role of Smarcad1 in retroviral silencing in ESCs. We show that Smarcad1 is immediately recruited to the MLV provirus. Based on the repression dynamics of a GFP-reporter MLV, our findings suggest that Smarcad1 plays a critical role in the establishment and maintenance of MLV repression, as well as other Trim28-targeted genomic loci. Furthermore, Smarcad1 is important for stabilizing and strengthening Trim28 binding to the provirus over time, and its presence around the provirus is needed for proper deposition of H3.3 on the provirus. Surprisingly, the combined depletion of Smarcad1 and Trim28 results in enhanced MLV derepression, suggesting that these two proteins may also function independently to maintain repressive chromatin states. Overall, the results of this study provide evidence for the crucial role of Smarcad1 in the silencing of retroviral elements in embryonic stem cells. Further research is needed to fully understand how Smarcad1 and Trim28 cooperate and their implications for gene expression and genomic stability.
小鼠胚胎干细胞(ESC)中的莫洛尼小鼠白血病病毒(MLV)复制受到Trim28-SETDB1复合物的抑制。染色质重塑者Smarcad1与Trim28相互作用,并被认为允许组蛋白变体H3.3的沉积。然而,Trim28、H3.3和Smarcad1在MLV抑制ESC中的作用仍有待全面了解。在这项研究中,我们利用MLV来探讨Smarcad1在ESC中逆转录病毒沉默中的作用。我们发现Smarcad1会被立即招募到MLV病毒上。基于GFP报告的MLV的抑制动态,我们的研究结果表明,Smarcad1在MLV抑制以及其他Trim28靶向基因组位点的建立和维持中起着关键作用。此外,随着时间的推移,Smarcad1 对稳定和加强 Trim28 与前病毒的结合非常重要,前病毒周围需要有 Smarcad1 才能使 H3.3 适当地沉积在前病毒上。令人惊讶的是,联合消耗 Smarcad1 和 Trim28 会增强 MLV 的抑制作用,这表明这两种蛋白也可能独立发挥作用,维持抑制性染色质状态。总之,本研究结果为Smarcad1在胚胎干细胞中沉默逆转录病毒元件的关键作用提供了证据。要全面了解Smarcad1和Trim28如何合作及其对基因表达和基因组稳定性的影响,还需要进一步的研究。
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引用次数: 0
CRISPR-TE: a web-based tool to generate single guide RNAs targeting transposable elements CRISPR-TE:生成针对转座元件的单导 RNA 的网络工具
IF 4.9 2区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-02-01 DOI: 10.1186/s13100-024-00313-0
Yixin Guo, Ziwei Xue, Meiting Gong, Siqian Jin, Xindi Wu, Wanlu Liu
The CRISPR/Cas systems have emerged as powerful tools in genome engineering. Recent studies highlighting the crucial role of transposable elements (TEs) have stimulated research interest in manipulating these elements to understand their functions. However, designing single guide RNAs (sgRNAs) that are specific and efficient for TE manipulation is a significant challenge, given their sequence repetitiveness and high copy numbers. While various sgRNA design tools have been developed for gene editing, an optimized sgRNA designer for TE manipulation has yet to be established. We present CRISPR-TE, a web-based application featuring an accessible graphical user interface, available at https://www.crisprte.cn/ , and currently tailored to the human and mouse genomes. CRISPR-TE identifies all potential sgRNAs for TEs and provides a comprehensive solution for efficient TE targeting at both the single copy and subfamily levels. Our analysis shows that sgRNAs targeting TEs can more effectively target evolutionarily young TEs with conserved sequences at the subfamily level. CRISPR-TE offers a versatile framework for designing sgRNAs for TE targeting. CRISPR-TE is publicly accessible at https://www.crisprte.cn/ as an online web service and the source code of CRISPR-TE is available at https://github.com/WanluLiuLab/CRISPRTE/ .
CRISPR/Cas 系统已成为基因组工程的强大工具。最近的研究强调了转座元件(TEs)的关键作用,激发了人们对操纵这些元件以了解其功能的研究兴趣。然而,考虑到转座元件的序列重复性和高拷贝数,设计特异且高效的单导RNA(sgRNA)来操纵转座元件是一项重大挑战。虽然已经开发出多种用于基因编辑的 sgRNA 设计工具,但用于 TE 操作的优化 sgRNA 设计器仍有待建立。我们介绍的 CRISPR-TE 是一种基于网络的应用程序,具有易于访问的图形用户界面,可通过 https://www.crisprte.cn/ 获取,目前专为人类和小鼠基因组定制。CRISPR-TE 可识别 TE 的所有潜在 sgRNA,并为单拷贝和亚家族水平的高效 TE 靶向提供全面的解决方案。我们的分析表明,靶向 TE 的 sgRNA 在亚家族水平上可以更有效地靶向具有保守序列的进化年轻 TE。CRISPR-TE 为设计用于 TE 靶向的 sgRNA 提供了一个多功能框架。CRISPR-TE 可在 https://www.crisprte.cn/ 上以在线网络服务的形式公开访问,CRISPR-TE 的源代码可在 https://github.com/WanluLiuLab/CRISPRTE/ 上获取。
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引用次数: 0
A systematic screen for co-option of transposable elements across the fungal kingdom 系统筛选真菌王国中的转座元件共用情况
IF 4.9 2区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-01-20 DOI: 10.1186/s13100-024-00312-1
Ursula Oggenfuss, Thomas Badet, Daniel Croll
How novel protein functions are acquired is a central question in molecular biology. Key paths to novelty include gene duplications, recombination or horizontal acquisition. Transposable elements (TEs) are increasingly recognized as a major source of novel domain-encoding sequences. However, the impact of TE coding sequences on the evolution of the proteome remains understudied. Here, we analyzed 1237 genomes spanning the phylogenetic breadth of the fungal kingdom. We scanned proteomes for evidence of co-occurrence of TE-derived domains along with other conventional protein functional domains. We detected more than 13,000 predicted proteins containing potentially TE-derived domain, of which 825 were identified in more than five genomes, indicating that many host-TE fusions may have persisted over long evolutionary time scales. We used the phylogenetic context to identify the origin and retention of individual TE-derived domains. The most common TE-derived domains are helicases derived from Academ, Kolobok or Helitron. We found putative TE co-options at a higher rate in genomes of the Saccharomycotina, providing an unexpected source of protein novelty in these generally TE depleted genomes. We investigated in detail a candidate host-TE fusion with a heterochromatic transcriptional silencing function that may play a role in TE and gene regulation in ascomycetes. The affected gene underwent multiple full or partial losses within the phylum. Overall, our work establishes a kingdom-wide view of putative host-TE fusions and facilitates systematic investigations of candidate fusion proteins.
如何获得新的蛋白质功能是分子生物学的一个核心问题。获得新功能的主要途径包括基因复制、重组或水平获取。可转座元件(Transposable elements,TE)越来越被认为是新型结构域编码序列的主要来源。然而,人们对可转座元件编码序列对蛋白质组进化的影响仍然缺乏研究。在这里,我们分析了横跨真菌王国系统发育广度的 1237 个基因组。我们扫描了蛋白质组,以寻找TE衍生结构域与其他常规蛋白质功能域共存的证据。我们检测到了 13,000 多种含有潜在 TE 衍生结构域的预测蛋白质,其中 825 种蛋白质在 5 个以上的基因组中被鉴定出来,这表明许多宿主与 TE 的融合可能在漫长的进化过程中持续存在。我们利用系统发育背景来确定单个 TE 衍生结构域的起源和保留情况。最常见的 TE 衍生结构域是源自 Academ、Kolobok 或 Helitron 的螺旋酶。我们在酵母科动物的基因组中发现了更高比例的假定 TE 共用,为这些普遍缺乏 TE 的基因组提供了意想不到的蛋白质新来源。我们详细研究了一个候选的宿主-TE融合基因,它具有异色转录沉默功能,可能在子囊菌的TE和基因调控中发挥作用。受影响的基因在该门中经历了多次完全或部分缺失。总之,我们的工作为推定的宿主-TE融合建立了一个全王国的视角,并促进了对候选融合蛋白的系统研究。
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引用次数: 0
Evolutionary dynamics of the LTR-retrotransposon crapaud in the Podospora anserina species complex and the interaction with repeat-induced point mutations Podospora anserina物种群中LTR-反转座子Crapaud的进化动态以及与重复诱导点突变的相互作用
IF 4.9 2区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-01-13 DOI: 10.1186/s13100-023-00311-8
Ivar Westerberg, S. Lorena Ament-Velásquez, Aaron A. Vogan, Hanna Johannesson
The genome of the filamentous ascomycete Podospora anserina shows a relatively high abundance of retrotransposons compared to other interspersed repeats. The LTR-retrotransposon family crapaud is particularly abundant in the genome, and consists of multiple diverged sequence variations specifically localized in the 5’ half of both long terminal repeats (LTRs). P. anserina is part of a recently diverged species-complex, which makes the system ideal to classify the crapaud family based on the observed LTR variation and to study the evolutionary dynamics, such as the diversification and bursts of the elements over recent evolutionary time. We developed a sequence similarity network approach to classify the crapaud repeats of seven genomes representing the P. anserina species complex into 14 subfamilies. This method does not utilize a consensus sequence, but instead it connects any copies that share enough sequence similarity over a set sequence coverage. Based on phylogenetic analyses, we found that the crapaud repeats likely diversified in the ancestor of the complex and have had activity at different time points for different subfamilies. Furthermore, while we hypothesized that the evolution into multiple subfamilies could have been a direct effect of escaping the genome defense system of repeat induced point mutations, we found this not to be the case. Our study contributes to the development of methods to classify transposable elements in fungi, and also highlights the intricate patterns of retrotransposon evolution over short timescales and under high mutational load caused by nucleotide-altering genome defense.
与其他穿插重复子相比,丝状无丝菌Podospora anserina的基因组显示出较高的反转座子丰度。LTR-retrotransposon 家族 crapaud 在基因组中的含量尤其丰富,它由多个不同的序列变异组成,特异性地定位于两个长末端重复序列(LTR)的 5' 半部。P.anserina是最近分化的物种复合体的一部分,这使得该系统非常适合根据观察到的LTR变异对crapaud家族进行分类,并研究其进化动态,如在最近的进化过程中元素的多样化和突变。我们开发了一种序列相似性网络方法,将代表P. anserina物种群的7个基因组中的Crapaud重复序列分为14个亚科。这种方法不使用共识序列,而是将在设定序列覆盖范围内具有足够序列相似性的拷贝连接起来。根据系统发生学分析,我们发现螯虾重复序列很可能在该复合体的祖先中发生了多样化,并在不同亚科的不同时间点具有活性。此外,虽然我们假设进化成多个亚家族可能是逃避重复点突变基因组防御系统的直接结果,但我们发现情况并非如此。我们的研究有助于开发真菌中转座元件的分类方法,同时也凸显了在核苷酸改变基因组防御系统造成的高突变负荷下,逆转录转座子在短时间内进化的复杂模式。
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引用次数: 0
The sixth Japanese meeting on biological function and evolution through interactions between hosts and transposable elements 第六次日本会议:通过宿主和转座元件之间的相互作用实现生物功能和进化
IF 4.9 2区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2023-12-12 DOI: 10.1186/s13100-023-00310-9
Kenji Ichiyanagi, Yoko Ikeda, Kuniaki Saito
The sixth Japanese meeting on host–transposon interactions, titled “Biological Function and Evolution through Interactions between Hosts and Transposable Elements,” was held on August 24th and 25th, 2023, at the National Institute of Genetics as well as online. This meeting was supported by the National Institute of Genetics and aimed to bring together researchers studying the diverse roles of TEs in genome function and evolution, as well as host defense systems against TE mobility, TE bursts during evolution, and intron mobility in mammals, insects, land plants, yeast, protozoa, and bacteria. Here, we have presented the highlights of the discussion. Organizers: Kenji Ichiyanagi, Yoko Ikeda, and Kuniaki Saito.
主题为 "通过宿主与可转座元件之间的相互作用实现生物功能与进化 "的第六次日本宿主与可转座元件相互作用会议于2023年8月24日和25日在国立遗传学研究所举行,并同时在线召开。本次会议由美国国家遗传学研究所(National Institute of Genetics)支持,旨在汇聚研究可转座元件在基因组功能和进化中的各种作用的研究人员,以及研究宿主对可转座元件流动性的防御系统、进化过程中的可转座元件突变以及哺乳动物、昆虫、陆生植物、酵母、原生动物和细菌中内含子流动性的研究人员。在此,我们将介绍讨论的重点内容。组织者:Kenji IchiyanagiKenji Ichiyanagi、Yoko Ikeda 和 Kuniaki Saito。
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引用次数: 0
SINE-derived satellites in scaled reptiles 鳞片爬行动物的 SINE 衍生卫星
IF 4.9 2区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2023-12-07 DOI: 10.1186/s13100-023-00309-2
Nikita S. Vassetzky, Sergei A. Kosushkin, Alexey P. Ryskov
The genomes of many eukaryotes contain DNA repeats in the form of both tandem and interspersed elements with distinct structure, evolutionary histories, and mechanisms of emergence and amplification. Although there is considerable knowledge regarding their diversity, there is little evidence directly linking these two types. Different tandem repeats derived from portions of short interspersed elements (SINEs) belonging to different families were identified in 56 genomes of squamate reptiles. All loci of SINE-derived satellites (sSats) were thoroughly analyzed. Snake sSats exhibited high similarity in both structure and copy number, while other taxa may have highly diverse (geckos), rare (Darevskia lizards), or missing sSats (agamid lizards). Similar to most satellites associated with heterochromatin, sSats are likely linked to subtelomeric chromosomal regions. Discovered tandem repeats derived from SINEs exhibit satellite-like properties, although they have not amplified to the same degree as typical satellites. The autonomous emergence of distinct sSats from diverse SINE families in numerous squamate species suggests a nonrandom process of satellite genesis originating from repetitive SINEs.
许多真核生物的基因组都含有串联和穿插两种形式的 DNA 重复序列,它们具有不同的结构、进化历史以及出现和扩增机制。尽管人们对它们的多样性有相当多的了解,但很少有证据能直接将这两种类型联系起来。在 56 个有鳞类爬行动物基因组中发现了不同的串联重复序列,这些序列来自属于不同家族的短穿插元件(SINE)。对 SINE 衍生卫星(sSats)的所有位点进行了深入分析。蛇类的 sSats 在结构和拷贝数方面都表现出高度的相似性,而其他类群的 sSats 可能具有高度的多样性(壁虎)、稀有性(Darevskia 蜥蜴)或缺失性(agamid 蜥蜴)。与大多数与异染色质相关的卫星类似,sSats 也可能与染色体次单粒体区域有关。发现的源自 SINEs 的串联重复序列具有类似卫星的特性,尽管它们的扩增程度不如典型的卫星。在众多有鳞类物种中,不同的 SINE 家族自主出现了不同的卫星,这表明卫星的形成过程并非随机,而是源于重复的 SINEs。
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引用次数: 0
An intronic LINE-1 regulates IFNAR1 expression in human immune cells. 内含子LINE-1调控人免疫细胞中IFNAR1的表达。
IF 4.9 2区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2023-11-30 DOI: 10.1186/s13100-023-00308-3
Carmen A Buttler, Daniel Ramirez, Robin D Dowell, Edward B Chuong

Background: Despite their origins as selfish parasitic sequences, some transposons in the human genome have been co-opted to serve as regulatory elements, contributing to the evolution of transcriptional networks. Most well-characterized examples of transposon-derived regulatory elements derive from endogenous retroviruses (ERVs), due to the intrinsic regulatory activity of proviral long terminal repeat regions. However, one subclass of transposable elements, the Long Interspersed Nuclear Elements (LINEs), have been largely overlooked in the search for functional regulatory transposons, and considered to be broadly epigenetically repressed.

Results: We examined the chromatin state of LINEs by analyzing epigenomic data from human immune cells. Many LINEs are marked by the repressive H3K9me3 modification, but a subset exhibits evidence of enhancer activity in human immune cells despite also showing evidence of epigenetic repression. We hypothesized that these competing forces of repressive and activating epigenetic marks might lead to inducible enhancer activity. We investigated a specific L1M2a element located within the first intron of Interferon Alpha/Beta Receptor 1 (IFNAR1). This element shows epigenetic signatures of B cell-specific enhancer activity, despite being repressed by the Human Silencing Hub (HUSH) complex. CRISPR deletion of the element in B lymphoblastoid cells revealed that the element acts as an enhancer that regulates both steady state and interferon-inducible expression of IFNAR1.

Conclusions: Our study experimentally demonstrates that an L1M2a element was co-opted to function as an interferon-inducible enhancer of IFNAR1, creating a feedback loop wherein IFNAR1 is transcriptionally upregulated by interferon signaling. This finding suggests that other LINEs may exhibit cryptic cell type-specific or context-dependent enhancer activity. LINEs have received less attention than ERVs in the effort to understand the contribution of transposons to the regulatory landscape of cellular genomes, but these are likely important, lineage-specific players in the rapid evolution of immune system regulatory networks and deserve further study.

背景:尽管它们起源于自私的寄生序列,但人类基因组中的一些转座子已被用作调控元件,促进了转录网络的进化。转座子衍生的调控元件的最典型的例子来自内源性逆转录病毒(erv),由于原病毒长末端重复区域的内在调控活性。然而,转座子的一个亚类,长分散核元件(LINEs),在寻找功能调节转座子的过程中很大程度上被忽视了,并且被认为是广泛的表观遗传抑制。结果:通过分析人类免疫细胞的表观基因组数据,我们检测了LINEs的染色质状态。许多细胞系被抑制的H3K9me3修饰标记,但是一个亚群在人类免疫细胞中表现出增强子活性的证据,尽管也显示出表观遗传抑制的证据。我们假设这些抑制和激活表观遗传标记的竞争力量可能导致诱导增强子活性。我们研究了位于干扰素α / β受体1 (IFNAR1)第一个内含子内的特定L1M2a元件。该元件显示了B细胞特异性增强子活性的表观遗传特征,尽管被Human Silencing Hub (HUSH)复合物抑制。CRISPR在B淋巴母细胞样细胞中删除该元件表明,该元件作为增强子调节IFNAR1的稳态和干扰素诱导表达。结论:我们的实验研究表明,L1M2a元件被增选为IFNAR1的干扰素诱导增强子,创建一个反馈回路,其中IFNAR1通过干扰素信号转录上调。这一发现表明,其他LINEs可能表现出隐细胞类型特异性或上下文依赖性增强子活性。在理解转座子对细胞基因组调控格局的贡献方面,LINEs受到的关注不如erv,但它们可能是免疫系统调控网络快速进化中重要的、谱系特异性的参与者,值得进一步研究。
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引用次数: 0
Meeting report: transposable elements at the crossroads of evolution, health and disease 2023. 会议报告:2023年在进化、健康和疾病的十字路口的转座因子。
IF 4.7 2区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2023-11-27 DOI: 10.1186/s13100-023-00307-4
Irina R Arkhipova, Kathleen H Burns, Katherine B Chiappinelli, Edward B Chuong, Clement Goubert, Alba Guarné, Amanda M Larracuente, E Alice Lee, Henry L Levin

The conference "Transposable Elements at the Crossroads of Evolution, Health and Disease" was hosted by Keystone Symposia in Whistler, British Columbia, Canada, on September 3-6, 2023, and was organized by Kathleen Burns, Harmit Malik and Irina Arkhipova. The central theme of the meeting was the incredible diversity of ways in which transposable elements (TEs) interact with the host, from disrupting the existing genes and pathways to creating novel gene products and expression patterns, enhancing the repertoire of host functions, and ultimately driving host evolution. The meeting was organized into six plenary sessions and two afternoon workshops with a total of 50 invited and contributed talks, two poster sessions, and a career roundtable. The topics ranged from TE roles in normal and pathological processes to restricting and harnessing TE activity based on mechanistic insights gained from genetic, structural, and biochemical studies.

“进化、健康和疾病十字路口的转座因子”会议于2023年9月3日至6日在加拿大不列颠哥伦比亚省惠斯勒由Keystone座谈会主办,由Kathleen Burns、Harmit Malik和Irina Arkhipova组织。会议的中心主题是转座因子(te)与宿主相互作用的方式的多样性,从破坏现有的基因和途径到创造新的基因产物和表达模式,增强宿主功能的曲目,并最终推动宿主进化。会议分为六个全体会议和两个下午讲习班,共有50个邀请和贡献的会谈,两个海报会议和一个职业圆桌会议。主题包括TE在正常和病理过程中的作用,以及基于遗传、结构和生化研究获得的机制见解来限制和利用TE活动。
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Mobile DNA
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