TABLE 3.

Epigenetic changes impacting livestock health.

Stimulus or disease	Breed	Organ	Epigenetic alteration	References
Environment stress
Heat stress (embryonic thermal manipulation)	Chicken; PB-2 and NN lines	Brain tissue (hypothalamus)	Altered methylation at HSPs	Kisliouk et al., 2017; Vinoth et al., 2018
Heat stress (embryonic thermal manipulation)	Broiler chickens	Hypothalamus and muscle tissues	785 H3K4me3 and 148 H3K27me3 differential peaks in the hypothalamus	David et al., 2019
Heat stress	Male DLY pigs	Longissimus dorsi muscles	57,147 DMRs corresponding to 1,422 DMGs	Hao et al., 2016
Heat stress	Hu sheep	Liver	Increased m6A on RNA of HSPs	Lu et al., 2019
Hypoxic stress (high and low altitude)	Tibetan pigs	Longissimus dorsi muscles	DMRs mainly involved in starch and sucrose metabolism	Jin L. et al., 2018
Hypoxic stress (different species and high/low altitude)	Tibetan and Yorkshire pigs	Heart	6,829, 11,997, 2,828, and 1,286 DMRs between TH vs YH, TL vs YL, TH vs TL, and YH vs YL	Zhang et al., 2019
Hypoxic stress (different species and highest plateau)	Tibetan goat, Tibetan sheep, Chuanzhong goat, and small-tailed Han sheep	Various tissues, including the heart, liver, lungs, kidney, muscle, and brain	Higher methylation in HIF-1α, HIF-3α, and EPO. Lower methylation rate in FIH-1	Wang et al., 2017g
Prenatal (transportation stress)	Brahman cows and their offspring	Blood	7,407 hyper- and 8,721 hypomethylated CpG sites, including 1,205 DMCs located within promoter regions	Littlejohn et al., 2018
Disease
Mycobacterium bovis infection	Holstein–Friesian cattle	CD4 + T cells	Genome-wide DNA methylation profile revealed 760 DMRs	Doherty et al., 2016
Mycobacterium bovis infection	In vitro	Alveolar macrophages	H3K4me3 is more prevalent in chromatin, at a genome-wide level in the infected group	Hall et al., 2019
Johne’s disease	Holstein cows	Ileum and ileum lymph node	2,000 DMCs and 205 DMRs in the ileum, 6,394 DMCs and 3,946 DMRs in ileum lymph node in response to Mycobacterium avium spp. paratuberculosis	Ibeagha-Awemu et al., 2020a,b
Clinical mastitis	Holstein cattle	Blood	Altered methylation of CD4	Wang et al., 2013; Usman et al., 2016
Clinical mastitis	Holstein cows	Mammary glands	Changed DNA methylation-regulated IL6R transcription	Zhang et al., 2018a
E. coil- and S. aureus-induced mastitis	Holstein cows	Mammary glands, peripheral blood	Genome-wide DNA methylation profile revealed a plethora of DMRs	Song et al., 2016; Sajjanar et al., 2019; Ju et al., 2020; Wang et al., 2020c; Wu et al., 2020b
E. coil-induced mastitis	Holstein cows	Lymphocytes	H3K27me3 levels in silent genes were higher in subclinical S. aureus mastitis cattle than in healthy cows	He et al., 2016
LPS challenge	Cows	Endometrial cells	Decreased methylation of specific CpG sites at IL-6; increased expression level of IL-6, IL-8, and DNMTs	Wang et al., 2018
LPS challenge	In vitro	Mammary epithelial cell	High LPS dose induced hypomethylation of immune-related genes, while low LPS dose induced hypermethylation of lactation-related genes	Chen J. et al., 2019
BVDV	In vitro	Madin–Darby bovine kidney cell	DNMT1 silencing induced decreased methylation level of miR-29b and repressed BVDV replication	Fu et al., 2017
Subacute ruminal acidosis	Dairy goat	Liver	Reduced promoter methylation level of LOC101896713 and CASP8	Chang et al., 2018
Scrapie	Sheep	Thalamus	8,907 DMRs	Hernaiz et al., 2019
Poly I:C stimulation	Dapulian and Landrace pigs	Peripheral blood mononuclear cell	5,827 DMRs and 70 DM and DE genes	Wang et al., 2017c
Bacteria colonization in intestine	Danish Landrace × Large White × Duroc pigs	Distal small intestine	Changed genome-wide DNA methylation related to the expression of immune genes	Pan et al., 2018, 2020
E. coli challenge	Sows	Mammary epithelial cells	561 and 898 DMCs at 3 and 24 h after E. coli challenge	Sajjanar et al., 2019
Porcine epidemic diarrhea virus	Large White piglets	Jejunum	Higher H3K4me3 enrichment and expression levels of some antiviral genes in the infected group	Wang H. et al., 2019
PRRSV	Transgenic pigs	serum and lung tissues	HDAC6 overexpression enhances resistance to PRRSV infection	Lu et al., 2017
H5N1 influenza virus	BWEL-SPF chicken	Spleen, thymus, and bursa of Fabricius	Significantly upregulated total DNA methylation levels in the thymus and bursa of the infected group	Zhang Y. et al., 2016
Salmonella enterica infection	Domestic chickens	Blood	879 DMRs including 135 DMRs in the promoter regions	Wang et al., 2017a
Marek’s disease	Two specific pathogen-free inbred lines of White Leghorn	Bursa of Fabricius	Different H3K27me3 markers associated with immune-related genes	Mitra et al., 2015; Song, 2016
NDV infection under heat stress condition	Fayoumi and Leghorn	Bursa	Greater differences in histone modification (H3K27ac and H3K4me1) levels in Leghorns than Fayoumis, associated genes enriched in biological processes gene ontology terms related to cell cycle and receptor signaling of lymphocytes	Chanthavixay et al., 2020b

H3K4me3, trimethylation at the fourth lysine residue of histone H3 protein; H3K27me3, trimethylation at the 27th lysine residue of histone H3 protein; DMR, differential methylated region; DMG, differential methylated gene; HSP, heat-shock protein; DMC, differential methylated CpG; TH, Tibetan pigs grown in the highland; TL, Tibetan pigs grown in the lowland; YH, Yorkshire pigs grown in the highland; YL, Yorkshire pigs grown in the lowland; E. coil, Escherichia coli; S. aureus, Staphylococcus aureus; LPS, lipopolysaccharide; BVDV, bovine viral diarrhea virus; PRRSV, porcine reproductive and respiratory syndrome virus; DM, differentially methylated, DE, differentially expressed; NDV, Newcastle disease virus; H3K27ac, acetylation at the 27th lysine residue of histone H3 protein; H3K4me1, the monomethylation at the fourth lysine residue of the histone H3 protein.