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一个自发的遗传诱导的反转座子上的表观等位基因塑造了宿主基因组的功能。

A spontaneous genetically induced epiallele at a retrotransposon shapes host genome function.

机构信息

Department of Genetics, University of Cambridge, Cambridge, United Kingdom.

出版信息

Elife. 2021 Mar 23;10:e65233. doi: 10.7554/eLife.65233.

DOI:10.7554/eLife.65233
PMID:33755012
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8084528/
Abstract

Intracisternal A-particles (IAPs) are endogenous retroviruses (ERVs) responsible for most insertional mutations in the mouse. Full-length IAPs harbour genes flanked by long terminal repeats (LTRs). Here, we identify a solo LTR IAP variant () recently formed in the inbred C57BL/6J mouse strain. In contrast to the C57BL/6J full-length IAP at this locus (), lacks DNA methylation and H3K9 trimethylation. The distinct DNA methylation levels between the two alleles are established during preimplantation development, likely due to loss of KRAB zinc finger protein binding at the variant. methylation increases and becomes more variable in a hybrid genetic background yet is unresponsive to maternal dietary methyl supplementation. Differential epigenetic modification of the two variants is associated with metabolic differences and tissue-specific changes in adjacent gene expression. Our characterisation of as a genetically induced epiallele with functional consequences establishes a new model to study transposable element repression and host-element co-evolution.

摘要

内含子 A 颗粒 (IAPs) 是内源性逆转录病毒 (ERVs)，负责小鼠中大多数插入突变。全长 IAPs 带有由长末端重复序列 (LTRs) 侧翼的基因。在这里，我们鉴定了一种最近在近交 C57BL/6J 小鼠品系中形成的单 LTR IAP 变体 ()。与该基因座上的 C57BL/6J 全长 IAP 相比 ()，缺乏 DNA 甲基化和 H3K9 三甲基化。两个等位基因之间的独特 DNA 甲基化水平是在着床前发育过程中建立的，可能是由于 KRAB 锌指蛋白在 变体上的结合丢失所致。 甲基化水平在杂种遗传背景中增加且变得更加多样化，但对母体膳食甲基供体补充无反应。两个变体的差异表观遗传修饰与代谢差异以及相邻基因表达的组织特异性变化相关。我们将 作为具有功能后果的遗传诱导的表观等位基因进行表征，为研究转座元件抑制和宿主元件共同进化建立了一个新模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa06/8084528/f6aaf573ed61/elife-65233-fig5-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa06/8084528/792aa86f7f40/elife-65233-fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa06/8084528/6248ba11320d/elife-65233-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa06/8084528/70c0d6fc3279/elife-65233-fig2-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa06/8084528/11ee907147ad/elife-65233-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa06/8084528/c6063e18dcf8/elife-65233-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa06/8084528/d834add68dfc/elife-65233-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa06/8084528/a542b68dae71/elife-65233-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa06/8084528/d410ced6783b/elife-65233-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa06/8084528/f6aaf573ed61/elife-65233-fig5-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa06/8084528/792aa86f7f40/elife-65233-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa06/8084528/cff56e20998a/elife-65233-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa06/8084528/4d8e68563aeb/elife-65233-fig1-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa06/8084528/3c295123c4e7/elife-65233-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa06/8084528/6248ba11320d/elife-65233-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa06/8084528/70c0d6fc3279/elife-65233-fig2-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa06/8084528/11ee907147ad/elife-65233-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa06/8084528/c6063e18dcf8/elife-65233-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa06/8084528/d834add68dfc/elife-65233-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa06/8084528/a542b68dae71/elife-65233-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa06/8084528/d410ced6783b/elife-65233-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa06/8084528/f6aaf573ed61/elife-65233-fig5-figsupp2.jpg

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