Kang Seong W, Madkour Mahmoud, Kuenzel Wayne J
Department of Poultry Science, Center of Excellence for Poultry Science, University of Arkansas, FayettevilleAR, United States.
Department of Animal Production, National Research CenterGiza, Egypt.
Front Genet. 2017 Dec 6;8:204. doi: 10.3389/fgene.2017.00204. eCollection 2017.
DNA methylation was reported as a possible stress-adaptation mechanism involved in the transcriptional regulation of stress responsive genes. Limited data are available on effects of psychological stress and early-life nutritional stress on DNA methylation regulators [DNMTs: DNA (cytosine-5)-methyltransferase 1 (DNMT1), DNMT1 associated protein (DMAP1), DNMT 3 alpha (DNMT3A) and beta (DNMT3B)] in avian species. The objectives of this study were to: (1) investigate changes in expression of DNMT1, DMAP1, DNMT3A, and DNMT3B following acute (AS) or chronic immobilization stress (CS); (2) test immediate effect of early-life nutritional stress [food deprivation (FD) for 12 h (12hFD) or 36 h (36hFD) at the post-hatching period] on expression of DNA methylation regulators and glucocorticoid receptor (GR), and the long-term effect of early-life nutritional stress at 6 weeks of age. Expression of DNMTs and plasma corticosterone (CORT) concentration decreased by CS compared to AS ( < 0.05), indicating differential roles of DNA methylation regulators in the stress response. Plasma CORT at 12hFD and 36hFD birds increased compared to control birds (12hF and 36hF), but there were no significant differences in plasma CORT of 12hFD and 36hFD birds at 6 weeks of age compared to 6 week controls. DNMT1, DMAP1, and DNMT3B expression in the anterior pituitary increased by 12hFD, but decreased at 36hFD compared to their controls ( < 0.05). In liver, DNMT1, DNMT3A, and DNMT3B expression decreased by 12hFD, however, no significant changes occurred at 36hFD. Expression of DMAP1, DNMT3A, and DNMT3B in anterior pituitary and DMAP1 and DNMT3A expression in liver at 6 weeks of age were higher in 36hFD stressed birds compared to controls as well as 12hFD stressed birds. Hepatic GR expression decreased by 12hFD and increased by 36hFD ( < 0.05). Expression patterns of GR in the liver of FD stress-induced birds persisted until 6 weeks of age, suggesting the possible lifelong involvement of liver GR in early-life nutritional stress response of birds. Taken together, results suggest that DNA methylation regulator genes are tissue-specifically responsive to acute and chronic stress, and hepatic GR may play a critical role in regulating the early-life nutritional stress response of birds. In addition, the downregulation of DNMT1 and DMAP1 may be one of the adaptive mechanisms to chronic early-life nutritional stress via passive demethylation.
据报道,DNA甲基化是一种可能参与应激反应基因转录调控的应激适应机制。关于心理应激和早期营养应激对鸟类DNA甲基化调节因子[DNA(胞嘧啶-5)-甲基转移酶1(DNMT1)、DNMT1相关蛋白(DMAP1)、DNMT 3α(DNMT3A)和β(DNMT3B)]影响的数据有限。本研究的目的是:(1)研究急性(AS)或慢性固定应激(CS)后DNMT1、DMAP1、DNMT3A和DNMT3B表达的变化;(2)测试早期营养应激[孵化后12小时(12hFD)或36小时(36hFD)食物剥夺(FD)]对DNA甲基化调节因子和糖皮质激素受体(GR)表达的即时影响,以及6周龄时早期营养应激的长期影响。与AS相比,CS使DNMTs的表达和血浆皮质酮(CORT)浓度降低(<0.05),表明DNA甲基化调节因子在应激反应中具有不同作用。与对照鸟(12hF和36hF)相比,12hFD和36hFD鸟的血浆CORT升高,但6周龄时12hFD和36hFD鸟的血浆CORT与6周龄对照相比无显著差异。与对照相比,12hFD使垂体前叶中DNMT1、DMAP1和DNMT3B的表达增加,但36hFD时降低(<0.05)。在肝脏中,12hFD使DNMT1、DNMT3A和DNMT3B的表达降低,但36hFD时无显著变化。与对照以及12hFD应激鸟相比,36hFD应激鸟在6周龄时垂体前叶中DMAP1、DNMT3A和DNMT3B的表达以及肝脏中DMAP1和DNMT3A的表达更高。肝脏GR表达在12hFD时降低,在36hFD时升高(<0.05)。FD应激诱导的鸟肝脏中GR的表达模式持续到6周龄,表明肝脏GR可能终生参与鸟类早期营养应激反应。综上所述,结果表明DNA甲基化调节基因对急性和慢性应激具有组织特异性反应,肝脏GR可能在调节鸟类早期营养应激反应中起关键作用。此外,DNMT1和DMAP1的下调可能是通过被动去甲基化对慢性早期营养应激的适应性机制之一。