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猪出生后肝发育过程中的 DNA 甲基化。

DNA Methylation of Postnatal Liver Development in Pigs.

机构信息

Key Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, Sichuan Agricultural University, Chengdu 611130, China.

College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.

出版信息

Genes (Basel). 2024 Aug 13;15(8):1067. doi: 10.3390/genes15081067.

DOI:10.3390/genes15081067
PMID:39202427
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11353940/
Abstract

DNA methylation plays an important role in the development and tissue differentiation of eukaryotes. In this study, bisulfite sequencing (BS-seq) technology was used to analyze the DNA methylation profiles of liver tissues taken from Rongchang pigs at three postnatal feeding stages, including newborn, suckling, and adult. The DNA methylation pattern across the genomes or genic region showed little difference between the three stages. We observed 419 differentially methylated regions (DMRs) in promoters, corresponding to 323 genes between newborn and suckling stages, in addition to 288 DMRs, corresponding to 134 genes, between suckling and adult stages and 351 DMRs, corresponding to 293 genes, between newborn and adult stages. These genes with DMRs were mainly enriched in metabolic, immune-related functional processes. Correlation analysis showed that the methylation level of gene promoters was significantly negatively correlated with gene expression. Further, we found that genes related to nutritional metabolism, e.g., carbohydrate metabolism (FAHD1 and GUSB) or fatty acid metabolism (LPIN1 and ACOX2), lost DNA methylation in their promoter, with mRNA expression increased in newborn pigs compared with those in the suckling stage. A few fatty acid metabolism-related genes (SLC27A5, ACOX2) were hypomethylated and highly expressed in the newborn stage, which might satisfy the nutritional requirements of Rongchang pigs with high neonatal birth rates. In the adult stage, HMGCS2-which is related to fatty acid β-oxidation-was hypomethylated and highly expressed, which explains that the characteristics of high energy utilization in adult Rongchang pigs and their immune-related genes (CD68, STAT2) may be related to the establishment of liver immunity. This study provides a comprehensive analysis of genome-wide DNA methylation patterns in pig liver postnatal development and growth. Our findings will serve as a valuable resource in hepatic metabolic studies and the agricultural food industry.

摘要

DNA 甲基化在真核生物的发育和组织分化中起着重要作用。在这项研究中,我们使用亚硫酸氢盐测序(BS-seq)技术分析了荣昌猪三个产后饲养阶段(新生、哺乳和成年)肝脏组织的 DNA 甲基化谱。整个基因组或基因区域的 DNA 甲基化模式在这三个阶段之间几乎没有差异。我们在新生和哺乳阶段之间观察到 419 个启动子差异甲基化区域(DMR),对应 323 个基因,在哺乳和成年阶段之间观察到 288 个 DMR,对应 134 个基因,在新生和成年阶段之间观察到 351 个 DMR,对应 293 个基因。这些具有 DMR 的基因主要富集在代谢、免疫相关的功能过程中。相关性分析表明,基因启动子的甲基化水平与基因表达呈显著负相关。此外,我们发现与营养代谢相关的基因,如碳水化合物代谢(FAHD1 和 GUSB)或脂肪酸代谢(LPIN1 和 ACOX2),其启动子的 DNA 甲基化丢失,mRNA 表达在新生仔猪中增加与哺乳阶段相比。一些脂肪酸代谢相关基因(SLC27A5、ACOX2)在新生阶段低甲基化且高表达,这可能满足荣昌仔猪高初生率的营养需求。在成年阶段,与脂肪酸β-氧化有关的 HMGCS2 低甲基化且高表达,这表明成年荣昌猪高能量利用的特点及其免疫相关基因(CD68、STAT2)可能与肝脏免疫的建立有关。本研究全面分析了猪肝脏产后发育和生长过程中的全基因组 DNA 甲基化模式。我们的研究结果将为肝代谢研究和农业食品工业提供有价值的资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b09f/11353940/529001e9113c/genes-15-01067-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b09f/11353940/0e5ed2fc2e64/genes-15-01067-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b09f/11353940/6e1859d5d5ba/genes-15-01067-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b09f/11353940/6640f858fc12/genes-15-01067-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b09f/11353940/529001e9113c/genes-15-01067-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b09f/11353940/0e5ed2fc2e64/genes-15-01067-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b09f/11353940/6e1859d5d5ba/genes-15-01067-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b09f/11353940/6640f858fc12/genes-15-01067-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b09f/11353940/529001e9113c/genes-15-01067-g004.jpg

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Sci Bull (Beijing). 2023 Nov 15;68(21):2583-2597. doi: 10.1016/j.scib.2023.09.021. Epub 2023 Sep 19.
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DNA Methylation of Genes Participating in Hepatic Metabolisms and Function in Fetal Calf Liver Is Altered by Maternal Undernutrition during Gestation.母体妊娠期间营养不良会改变胎牛肝脏中参与肝脏代谢和功能的基因的 DNA 甲基化。
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J Interferon Cytokine Res. 2022 Sep;42(9):467-481. doi: 10.1089/jir.2022.0117. Epub 2022 Jul 25.
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Transcriptomic Profile of the Mouse Postnatal Liver Development by Single-Nucleus RNA Sequencing.通过单核RNA测序对小鼠出生后肝脏发育的转录组图谱分析
Front Cell Dev Biol. 2022 Apr 6;10:833392. doi: 10.3389/fcell.2022.833392. eCollection 2022.
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Genomics. 2022 May;114(3):110342. doi: 10.1016/j.ygeno.2022.110342. Epub 2022 Mar 17.
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Development. 2022 Jan 15;149(2). doi: 10.1242/dev.200118. Epub 2022 Jan 20.
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