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 (BMDMs). 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 and will provide new insights for immunotherapy in macrophage-associated diseases.
- Abbreviations
- LncRNA
- Long non-coding RNA
- Dnmt3aos
- DNA methyltransferase 3A opposite strand
- Dnmt3a
- DNA methyltransferase 3a
- BMDM
- bone marrow-derived macrophages
- MeDIP-seq
- methylated DNA immunoprecipitation sequencing
- LPS
- lipopolysaccharides
- IFN-γ
- interferon-gamma
- GM-CSF
- granulocyte-macrophage colony stimulating factor
- IL-4
- interleukin-4
- IL-12
- interleukin-12
- IL-13
- interleukin-13
- TNF-α
- tumor necrosis factor alpha
- NO
- nitric oxide
- CD80
- cluster of differentiation 80
- CD68
- cluster of differentiation 68
- M-CSF
- macrophage colony stimulating factors
- TGF-β
- transforming growth factor beta-1
- Arg-1
- Arginase 1
- YM1
- chitinase 3-like 3
- Fizz1
- Resistin-like-α
- DMR
- differentially methylated region
- UTR
- untranslated region
- CDS
- coding sequence
- TTR
- transcriptional termination region
- GO
- gene ontology
- DEG
- differentially expressed gene
- 5-Aza-CdR
- 5-Aza-2’-deoxycytidine
- BSP
- bisulfite sequencing PCR
- ncRNA
- non-coding RNA.