Identification of DNMT3B2 as the Predominant Isoform of DNMT3B in Porcine Alveolar Macrophages and Its Involvement in LPS-Stimulated TNF-alpha Expression

文献类型： 外文期刊

第一作者： Zhang, Yanbing

作者： Zhang, Yanbing;Li, Hui;Xiang, Xiao;Lu, Yan;Sharma, Mona;Li, Zongjie;Liu, Ke;Wei, Jianchao;Shao, Donghua;Li, Beibei;Ma, Zhiyong;Qiu, Yafeng

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关键词： porcine alveolar macrophages; DNMT3B; DNA methylation; isoform; TNF-α

期刊名称：GENES （ 影响因子：4.096； 五年影响因子：4.339 ）

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年卷期： 2020 年 11 卷 9 期

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收录情况： SCI

摘要： DNA methyltransferase 3B (DNMT3B) as one member of the DNMT family functions as a de novo methyltransferase, characterized as more than 30 splice variants in humans and mice. However, the expression patterns of DNMT3B in pig as well as the biological function of porcine DNMT3B remain to be determined. In this study, we first examined the expression patterns of DNMT3B in porcine alveolar macrophages (PAM). We demonstrated that only DNMT3B2 and DNMT3B3 were the detectable isoforms in PAM. Furthermore, we revealed that DNTM3B2 was the predominant isoform in PAM. Next, in the model of LPS (lipopolysaccharide)-activated PAM, we showed that in comparison to the unstimulated PAM, (1) expression of DNTM3B is reduced; (2) the methylation level of TNF-alpha gene promoter is decreased. We further establish that DNMT3B2-mediated methylation of TNF-alpha gene promoter restricts induction of TNF-alpha in the LPS-stimulated PAM. In summary, these findings reveal that DNMT3B2 is the predominant isoform in PAM and its downregulation contributes to expression of TNF-alpha via hypomethylation of TNF-alpha gene promoter in the LPS-stimulated PAM.

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