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猪在产前和产后补充膳食ω-3脂肪酸后的全基因组甲基化图谱。

Genome-wide methylation profile following prenatal and postnatal dietary omega-3 fatty acid supplementation in pigs.

作者信息

Boddicker R L, Koltes J E, Fritz-Waters E R, Koesterke L, Weeks N, Yin T, Mani V, Nettleton D, Reecy J M, Baumgard L H, Spencer J D, Gabler N K, Ross J W

机构信息

Department of Animal Science, Iowa State University, Ames, IA, 50011, USA.

Texas Advanced Computing Center, University of Texas, Austin, TX, 78758-4497, USA.

出版信息

Anim Genet. 2016 Dec;47(6):658-671. doi: 10.1111/age.12468. Epub 2016 Aug 25.

Abstract

The objective of this study was to determine how prenatal and postnatal dietary omega-3 fatty acids alter white blood cell (leukocyte) DNA methylation of offspring. Fifteen gilts (n = 5 per treatment) were selected from one of three treatments: (i) control diet throughout gestation, lactation and nursery phase (CON); (ii) algal omega-3 fatty acid supplementation enriched in EPA and DHA (Gromega ) fed throughout gestation, lactation and nursery phase (Cn3); or (iii) Gromega supplementation maternally, during gestation and lactation only, and control diet during the nursery phase (Mn3). At 11 weeks of age and after 8 weeks of post-weaning nursery feeding, buffy coat genomic DNA was subjected to methyl CpG binding protein sequencing. The methylation enriched profile mapped to 26% of the porcine genome. On chromosome 4, a 27.7-kb differentially methylated region downstream of RUNX1T1 was hypomethylated in the Mn3 and Cn3 groups by 91.6% and 85.0% respectively compared to CON pigs. Conversely, hypermethylation was detected in intergenic regions of chromosomes 4 and 12. Regulatory impact factor and differential hubbing methods were used to identify pathways that were coordinately regulated by methylation due to feeding EPA and DHA during pregnancy. Despite limited ability to detect differential methylation, we describe methods that allow the identification of coordinated epigenetic regulation that could not otherwise be detected from subtle single locus changes in methylation. These data provide evidence of novel epigenetic regulation by maternal and early life supplementation of omega-3 fatty acids that may have implications to growth and inflammatory processes.

摘要

本研究的目的是确定产前和产后饮食中的ω-3脂肪酸如何改变后代白细胞(白细胞)DNA甲基化。从三种处理中的一种中选择15头后备母猪(每组n = 5):(i)在整个妊娠期、哺乳期和保育期采用对照日粮(CON);(ii)在整个妊娠期、哺乳期和保育期饲喂富含二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)的藻类ω-3脂肪酸补充剂(Gromega)(Cn3);或(iii)仅在妊娠期和哺乳期母体补充Gromega,保育期采用对照日粮(Mn3)。在11周龄以及断奶后保育期饲喂8周后,对血沉棕黄层基因组DNA进行甲基化CpG结合蛋白测序。甲基化富集图谱覆盖了26%的猪基因组。在4号染色体上,RUNX1T1下游一个27.7 kb的差异甲基化区域,与CON组猪相比,Mn3组和Cn3组分别低甲基化91.6%和85.0%。相反,在4号和12号染色体的基因间区域检测到高甲基化。使用调控影响因子和差异中心性方法来识别由于孕期饲喂EPA和DHA而由甲基化协同调控的通路。尽管检测差异甲基化的能力有限,但我们描述了一些方法,这些方法能够识别出从甲基化的细微单基因座变化中无法检测到的协同表观遗传调控。这些数据提供了证据,表明母体和生命早期补充ω-3脂肪酸可产生新的表观遗传调控,这可能对生长和炎症过程产生影响。

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