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基因座水平 L1 DNA 甲基化分析揭示了 L1 与其整合位点之间的表观遗传和转录相互作用。

Locus-level L1 DNA methylation profiling reveals the epigenetic and transcriptional interplay between L1s and their integration sites.

机构信息

University Cote d'Azur, INSERM, CNRS, Institute for Research on Cancer and Aging of Nice (IRCAN), Nice, France.

University Paris Cité, CNRS, Epigenetics and Cell Fate, Paris, France.

出版信息

Cell Genom. 2024 Feb 14;4(2):100498. doi: 10.1016/j.xgen.2024.100498. Epub 2024 Feb 2.

DOI:10.1016/j.xgen.2024.100498
PMID:38309261
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10879037/
Abstract

Long interspersed element 1 (L1) retrotransposons are implicated in human disease and evolution. Their global activity is repressed by DNA methylation, but deciphering the regulation of individual copies has been challenging. Here, we combine short- and long-read sequencing to unveil L1 methylation heterogeneity across cell types, families, and individual loci and elucidate key principles involved. We find that the youngest primate L1 families are specifically hypomethylated in pluripotent stem cells and the placenta but not in most tumors. Locally, intronic L1 methylation is intimately associated with gene transcription. Conversely, the L1 methylation state can propagate to the proximal region up to 300 bp. This phenomenon is accompanied by the binding of specific transcription factors, which drive the expression of L1 and chimeric transcripts. Finally, L1 hypomethylation alone is typically insufficient to trigger L1 expression due to redundant silencing pathways. Our results illuminate the epigenetic and transcriptional interplay between retrotransposons and their host genome.

摘要

长散在元件 1（L1）逆转录转座子与人类疾病和进化有关。它们的整体活性受到 DNA 甲基化的抑制，但破译单个拷贝的调控一直具有挑战性。在这里，我们结合短读和长读测序来揭示细胞类型、家族和个体基因座中 L1 甲基化的异质性，并阐明所涉及的关键原则。我们发现，最年轻的灵长类 L1 家族在多能干细胞和胎盘组织中特异性低甲基化，但在大多数肿瘤中没有。局部来看，内含子 L1 的甲基化与基因转录密切相关。相反，L1 的甲基化状态可以传播到近端区域，长达 300bp。这种现象伴随着特定转录因子的结合，这些转录因子驱动 L1 和嵌合转录本的表达。最后，由于沉默途径的冗余，L1 低甲基化本身通常不足以触发 L1 表达。我们的研究结果阐明了逆转录转座子与其宿主基因组之间的表观遗传和转录相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a296/10879037/46e70b12dd9e/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a296/10879037/704693d56bca/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a296/10879037/588702843d51/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a296/10879037/e9786a9afa68/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a296/10879037/6c4c301f3983/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a296/10879037/924c2cd14412/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a296/10879037/8b2c02dcf29d/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a296/10879037/693c5974ac42/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a296/10879037/46e70b12dd9e/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a296/10879037/704693d56bca/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a296/10879037/588702843d51/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a296/10879037/e9786a9afa68/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a296/10879037/6c4c301f3983/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a296/10879037/924c2cd14412/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a296/10879037/8b2c02dcf29d/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a296/10879037/693c5974ac42/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a296/10879037/46e70b12dd9e/gr7.jpg

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3
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Blood Cancer J. 2025 May 6;15(1):87. doi: 10.1038/s41408-025-01295-9.
4
Age and Sex Effects on Blood Retrotransposable Element Expression Levels: Findings From the Population-Based Rhineland Study.年龄和性别对血液逆转录转座元件表达水平的影响：基于人群的莱茵兰研究结果
Aging Cell. 2025 Aug;24(8):e70092. doi: 10.1111/acel.70092. Epub 2025 May 4.
5
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NPJ Precis Oncol. 2025 Mar 6;9(1):62. doi: 10.1038/s41698-025-00849-1.
6
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Clin Epigenetics. 2025 Jan 16;17(1):7. doi: 10.1186/s13148-025-01815-1.
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