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绵羊不同组织及不同时间的全基因组DNA甲基化率变异性

Variability in Global DNA Methylation Rate Across Tissues and Over Time in Sheep.

作者信息

Drouilhet Laurence, Moreno Carole, Plisson-Petit Florence, Marcon Didier, Fabre Stéphane, Hazard Dominique

机构信息

GenPhySE, Université de Toulouse, INRAE, ENVT, Castanet-Tolosan, France.

P3R, UE 0332, INRAE, Osmoy, France.

出版信息

Front Genet. 2022 Mar 11;13:791283. doi: 10.3389/fgene.2022.791283. eCollection 2022.

DOI:10.3389/fgene.2022.791283
PMID:35360841
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8961874/
Abstract

Recent studies highlighted the influence of epigenetic marks in the variability of many complex traits, both in plants and animals. These studied focused only on specific sites of the genome having differentially methylated profiles among individuals and/or tissues. In contrast, we recently used the methylation rate of the entire genome as a unique measure considered as a novel quantitative phenotype in sheep. This phenotype named global DNA methylation rate (GDMR), measured by luminometric assay, integrates the methylation level of each CpG dinucleotide within the 6 million of CCGG sites along the ovine genome. GDMR measured in blood previously showed moderate heritability of 0.20 and provided evidence for a genetic determinism. The main objective of the present study was to better characterize the GDMR phenotype in various tissues and investigate its variability in several breeds of sheep reared in the same environment. GDMR was measured on blood samples collected monthly from 59 growing male and female lambs (24 Romane, 23 Blackbelly and 12 Charollais), between birth and 4 months of age. Blood GDMR was on average around 80% and was influenced by the sampling date ( < 0.001), the breed ( = 0.002) and the sex ( = 0.002). In addition, GDMR was determined in 12 somatic (frontal lobe, pituitary gland, heart, lung, sub cutaneous and perirenal adipose tissue, skeletal muscle, liver, spleen, adrenal gland, medulla and cortical kidney) and 6 reproductive tissues (ovary, oviduct, uterus, testis, epididymis and seminal vesicle). GDMR was on average 70% in somatic tissues but marked variation was observed depending on the tissue. The GDMR measured in blood was higher than that measured in other somatic tissues, and is not a good proxy of less accessible tissues. Female reproductive tissues had a 10% higher GDMR than male reproductive tissues. We demonstrated a significant influence of the breed on blood GDMR, certainly reflecting the influence of different genetic backgrounds. The effect of the breed on GDMR may be related to their specific abilities to adapt to and live in different conditions.

摘要

最近的研究突出了表观遗传标记对动植物许多复杂性状变异性的影响。这些研究仅聚焦于基因组中在个体和/或组织间具有不同甲基化谱的特定位点。相比之下,我们最近将整个基因组的甲基化率作为一种独特的度量,视为绵羊的一种新的定量表型。这种名为全基因组DNA甲基化率(GDMR)的表型通过发光测定法测量,整合了绵羊基因组中600万个CCGG位点内每个CpG二核苷酸的甲基化水平。先前在血液中测得的GDMR显示出0.20的中等遗传力,并为遗传决定论提供了证据。本研究的主要目的是更好地表征不同组织中的GDMR表型,并研究其在同一环境中饲养的几个绵羊品种中的变异性。在出生至4月龄期间,每月从59只生长中的雄性和雌性羔羊(24只罗曼羊、23只黑腹羊和12只夏洛莱羊)采集血液样本测量GDMR。血液GDMR平均约为80%,受采样日期(P<0.001)、品种(P = 0.002)和性别(P = 0.002)影响。此外,在12种体细胞组织(额叶、垂体、心脏、肺、皮下和肾周脂肪组织、骨骼肌、肝脏、脾脏、肾上腺、髓质和皮质肾)和6种生殖组织(卵巢、输卵管、子宫、睾丸、附睾和精囊)中测定了GDMR。体细胞组织中的GDMR平均为70%,但根据组织不同观察到明显差异。血液中测得的GDMR高于其他体细胞组织中的GDMR,并且不是难以获取组织的良好替代指标。雌性生殖组织的GDMR比雄性生殖组织高10%。我们证明了品种对血液GDMR有显著影响,这肯定反映了不同遗传背景的影响。品种对GDMR的影响可能与其适应和生活在不同条件下的特定能力有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d95/8961874/45aae31d92f0/fgene-13-791283-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d95/8961874/f814eb62949f/fgene-13-791283-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d95/8961874/d59b520bf139/fgene-13-791283-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d95/8961874/45aae31d92f0/fgene-13-791283-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d95/8961874/f814eb62949f/fgene-13-791283-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d95/8961874/d59b520bf139/fgene-13-791283-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d95/8961874/45aae31d92f0/fgene-13-791283-g003.jpg

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Castration delays epigenetic aging and feminizes DNA methylation at androgen-regulated loci.去势延缓表观遗传衰老,并使雄激素调控的基因座上的 DNA 甲基化向雌性化方向转变。
Elife. 2021 Jul 6;10:e64932. doi: 10.7554/eLife.64932.
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Genetic Determinism Exists for the Global DNA Methylation Rate in Sheep.绵羊全球DNA甲基化率存在遗传决定因素。
Front Genet. 2020 Dec 23;11:616960. doi: 10.3389/fgene.2020.616960. eCollection 2020.
3
DNA methylation enables transposable element-driven genome expansion.DNA 甲基化使转座元件驱动的基因组扩张成为可能。
Proc Natl Acad Sci U S A. 2020 Aug 11;117(32):19359-19366. doi: 10.1073/pnas.1921719117. Epub 2020 Jul 27.
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Comparative whole genome DNA methylation profiling across cattle tissues reveals global and tissue-specific methylation patterns.比较牛组织中的全基因组 DNA 甲基化图谱揭示了全局和组织特异性的甲基化模式。
BMC Biol. 2020 Jul 6;18(1):85. doi: 10.1186/s12915-020-00793-5.
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Analysis of DNA methylation profiles during sheep skeletal muscle development using whole-genome bisulfite sequencing.利用全基因组亚硫酸氢盐测序分析绵羊骨骼肌发育过程中的 DNA 甲基化图谱。
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