title: Epigenetic Regulation of miR-29s Affects the Lactation Activity of Dairy Cow Mammary Epithelial Cells.
abstract: Milk is important for human nutrition, and enhanced milk quality has become a major selection criterion for the genetic improvement of livestock. Epigenetic modifications have been shown to be involved in mammary gland development; but the mechanisms underlying their effects remain unknown. MicroRNAs are involved in the regulation of milk synthesis and in mammary gland development. Our study is the first to investigate the roles of miR-29s and epigenetic regulation in dairy cow mammary epithelial cells (DCMECs). Our results show that miR-29s regulate the DNA methylation level by inversely targeting both DNMT3A and DNMT3B in DCMECs. The inhibition of miR-29s caused global DNA hypermethylation and increased the methylation levels of the promoters of important lactation-related genes, including casein alpha s1 (CSN1S1), E74-like factor 5 (ElF5), peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element binding protein-1 (SREBP1), and glucose transporter 1 (GLUT1). The inhibition of miR-29s reduced the secretion of lactoprotein, triglycerides (TG) and lactose by DCMECs. Moreover, the treatment of DCMECs with 5-aza-2'-deoxycytidine (5-Aza-dC) decreased the methylation levels of the miR-29b promoter and increased the expression of miR-29b. The link between miR-29s and DNMT3A/3B enhances our understanding of the roles of miRNAs in mammary gland function, and our data will inform more experimentally oriented studies to identify new mechanisms of regulating lactation. We present new insights regarding the epigenetic regulation of lactation performance. Improved understanding of the molecular basis of lactation will aid in the development of strategies for optimizing milk quality in dairy cows and modifying the lactation performance of offspring.
authors: Research Department of Lactation Biology and Regulation of Mammary Gland Function, Northeast Agricultural University, Harbin, 150030, China.
authors: Yanjie
authors: Y
authors: Bian
authors: Research Department of Lactation Biology and Regulation of Mammary Gland Function, Northeast Agricultural University, Harbin, 150030, China.
authors: Yu
authors: Y
authors: Lei
authors: Key Laboratory of Dairy Science of Ministry of Education, Northeast Agricultural University, Harbin, 150030, China.
authors: Chunmei
authors: C
authors: Wang
authors: Key Laboratory of Dairy Science of Ministry of Education, Northeast Agricultural University, Harbin, 150030, China.
authors: Jie
authors: J
authors: Wang
authors: Research Department of Lactation Biology and Regulation of Mammary Gland Function, Northeast Agricultural University, Harbin, 150030, China.
authors: Lina
authors: L
authors: Wang
authors: Key Laboratory of Dairy Science of Ministry of Education, Northeast Agricultural University, Harbin, 150030, China.
authors: Lili
authors: L
authors: Liu
authors: Key Laboratory of Dairy Science of Ministry of Education, Northeast Agricultural University, Harbin, 150030, China.
authors: Lixin
authors: L
authors: Liu
authors: Key Laboratory of Dairy Science of Ministry of Education, Northeast Agricultural University, Harbin, 150030, China.
authors: Xuejun
authors: X
authors: Gao
authors: Research Department of Lactation Biology and Regulation of Mammary Gland Function, Northeast Agricultural University, Harbin, 150030, China.|Key Laboratory of Dairy Science of Ministry of Education, Northeast Agricultural University, Harbin, 150030, China.
authors: Qingzhang
authors: Q
authors: Li
mesh_terms: D000818:Animals; D002417:Cattle; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics; D000090205:DNA Methyltransferase 3A; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007774:Lactation; D008321:Mammary Glands, Animal / Q000378:metabolism*; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008892:Milk / Q000378:metabolism*
chemical_list: C000717967:DNMT3A protein, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A