RepEnTools: an automated repeat enrichment analysis package for ChIP-seq data reveals hUHRF1 Tandem-Tudor domain enrichment in young repeats

IF 4.7 2区 生物学 Q1 GENETICS & HEREDITY Mobile DNA Pub Date : 2024-04-03 DOI:10.1186/s13100-024-00315-y
Michel Choudalakis, Pavel Bashtrykov, Albert Jeltsch
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Abstract

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.
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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
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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来源期刊
Mobile DNA
Mobile DNA GENETICS & HEREDITY-
CiteScore
8.20
自引率
6.10%
发文量
26
审稿时长
11 weeks
期刊介绍: Mobile DNA is an online, peer-reviewed, open access journal that publishes articles providing novel insights into DNA rearrangements in all organisms, ranging from transposition and other types of recombination mechanisms to patterns and processes of mobile element and host genome evolution. In addition, the journal will consider articles on the utility of mobile genetic elements in biotechnological methods and protocols.
期刊最新文献
International congress on transposable elements (ICTE 2024) in Saint Malo: breaking down transposon waves and their impact. Accelerating de novo SINE annotation in plant and animal genomes. Association of hyperactivated transposon expression with exacerbated immune activation in systemic lupus erythematosus. Widespread HCD-tRNA derived SINEs in bivalves rely on multiple LINE partners and accumulate in genic regions. Correction: Transposon-derived introns as an element shaping the structure of eukaryotic genomes.
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