LncRNA Dnmt3aos regulates Dnmt3a expression leading to aberrant DNA methylation in macrophage polarization

FASEB J. 2020 Apr;34(4):5077-5091. doi: 10.1096/fj.201902379R. Epub 2020 Feb 13.

Abstract

Long non-coding RNAs (lncRNAs) play key roles in various biological processes. However, the roles of lncRNAs in macrophage polarization remain largely unexplored. In this study, thousands of lncRNAs were identified that are differentially expressed in distinct polarized bone marrow-derived macrophages. Among them, Dnmt3aos (DNA methyltransferase 3A, opposite strand), as a known lncRNA, locates on the antisense strand of Dnmt3a. Functional experiments further confirmed that Dnmt3aos were highly expressed in M(IL-4) macrophages and participated in the regulation of Dnmt3a expression, and played a key role in macrophage polarization. The DNA methylation profiles between the Dnmt3aos knockdown group and the control group in M(IL-4) macrophages were determined by MeDIP-seq technique for the first time, and the Dnmt3aos-Dnmt3a axis-mediated DNA methylation modification-regulated macrophage polarization- related gene IFN-γ was identified. Our study will help to enrich our knowledge of the mechanism of macrophage polarization.

Keywords: DNA methylation; Dnmt3a; LncRNA; macrophage polarization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methylation*
  • DNA Methyltransferase 3A
  • Interferon-gamma / metabolism
  • Macrophages / cytology
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • RNA, Antisense / genetics*
  • RNA, Antisense / metabolism
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism

Substances

  • Dnmt3a protein, mouse
  • RNA, Antisense
  • RNA, Long Noncoding
  • Interferon-gamma
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A