title: Maternal high-zinc diet attenuates intestinal inflammation by reducing DNA methylation and elevating H3K9 acetylation in the A20 promoter of offspring chicks.
abstract: A20 is an anti-inflammatory protein that suppresses ubiquitin-dependent nuclear factor κB (NF-κB) signaling, which can be regulated by the microelement zinc (Zn). In mammals, Zn deficiency contributes to a decrease in A20 abundance, which impairs the gut mucosa barrier. However, it is unclear whether the epigenetic reprogramming of the A20 promoter is involved in enhanced Zn-induced intestinal immunity, especially in avian species. Herein, we show that maternal organic Zn exposure resulted in significantly improved intestinal morphological characteristics, increased mucin 2 (MUC2) abundance and secretory IgA (sIgA) production in progeny jejunums. Maternal and offspring Zn supplementation partially alleviated Zn-deficiency-induced inflammatory response, accompanied by repression of NF-κB signaling. Additionally, we observed DNA hypomethylation and histone H3 at lysine 9 (H3K9) hyperacetylation at the A20 promoter region and subsequent activated A20 expression in Zn-supplemented hens compared with control. Notably, maternal dietary organic Zn exposure exhibited greater attenuation of gut impairment, along with increased MUC2 expression and sIgA level, and decreased the abundance of TNF-α and A20 relative to the inorganic-Zn group. Furthermore, enhanced acetylated H3K9 and A20 transcription at day 14 was found in the offspring adequate dietary Zn group. Thus, A20 may be a novel inflammatory-suppressed factor of chick gut that is persistently promoted by dietary Zn supplementation via epigenetic modifications at A20 promoter.
authors.affiliation: State key Laboratory of Animal Nutrition, Hubei Collaborative Innovation Center for Animal Nutrition and Feed Science, College of Animal Science and Technology, China Agricultural University, Beijing, Yuanmingyuan West Road, Haidian District, Beijing, People's Republic of China, 100193.
authors.forename: Changwu
authors.initials: C
authors.lastname: Li
authors.affiliation: State key Laboratory of Animal Nutrition, Hubei Collaborative Innovation Center for Animal Nutrition and Feed Science, College of Animal Science and Technology, China Agricultural University, Beijing, Yuanmingyuan West Road, Haidian District, Beijing, People's Republic of China, 100193.
authors.forename: Shuangshuang
authors.initials: S
authors.lastname: Guo
authors.affiliation: State key Laboratory of Animal Nutrition, Hubei Collaborative Innovation Center for Animal Nutrition and Feed Science, College of Animal Science and Technology, China Agricultural University, Beijing, Yuanmingyuan West Road, Haidian District, Beijing, People's Republic of China, 100193.
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.affiliation: State key Laboratory of Animal Nutrition, Hubei Collaborative Innovation Center for Animal Nutrition and Feed Science, College of Animal Science and Technology, China Agricultural University, Beijing, Yuanmingyuan West Road, Haidian District, Beijing, People's Republic of China, 100193. Electronic address: guoyum@cau.edu.cn.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Guo
authors.affiliation: State key Laboratory of Animal Nutrition, Hubei Collaborative Innovation Center for Animal Nutrition and Feed Science, College of Animal Science and Technology, China Agricultural University, Beijing, Yuanmingyuan West Road, Haidian District, Beijing, People's Republic of China, 100193.
authors.forename: Encun
authors.initials: E
authors.lastname: Du
authors.affiliation: State key Laboratory of Animal Nutrition, Hubei Collaborative Innovation Center for Animal Nutrition and Feed Science, College of Animal Science and Technology, China Agricultural University, Beijing, Yuanmingyuan West Road, Haidian District, Beijing, People's Republic of China, 100193.
authors.forename: Zengpeng
authors.initials: Z
authors.lastname: Lv
authors.affiliation: State key Laboratory of Animal Nutrition, Hubei Collaborative Innovation Center for Animal Nutrition and Feed Science, College of Animal Science and Technology, China Agricultural University, Beijing, Yuanmingyuan West Road, Haidian District, Beijing, People's Republic of China, 100193.
authors.forename: Beibei
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000107:Acetylation; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017849:Animals, Inbred Strains; D030161:Avian Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001715:Bird Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002645:Chickens; D002681:China; D019175:DNA Methylation; D003677:Deficiency Diseases / Q000178:diet therapy / Q000503:physiopathology / Q000662:veterinary; D004032:Diet / Q000662:veterinary*; D004751:Enteritis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control / Q000662:veterinary*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000378:metabolism*; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007583:Jejunum / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D015032:Zinc / Q000008:administration & dosage / Q000172:deficiency / Q000627:therapeutic use*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D030161:Avian Proteins; D006657:Histones; D015032:Zinc
keywords: Chicken; Cytokines; Inflammation; Mucosal immunity; Small intestine