PT  - JOURNAL ARTICLE
AU  - Xueqin Li
AU  - Yingying Zhang
AU  - Mengying Zhang
AU  - Xiang Kong
AU  - Hui Yang
AU  - Min Zhong
AU  - Weiya Pei
AU  - Yang Xu
AU  - Xiaolong Zhu
AU  - Tianbing Chen
AU  - Jingjing Ye
AU  - Kun Lv
TI  - LncRNA <em>Dnmt3aos</em> regulates <em>Dnmt3a</em> expression leading to aberrant DNA methylation in macrophage polarization
AID  - 10.1101/514307
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 514307
4099  - http://biorxiv.org/content/early/2019/01/07/514307.short
4100  - http://biorxiv.org/content/early/2019/01/07/514307.full
AB  - 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.AbbreviationsLncRNALong non-coding RNADnmt3aosDNA methyltransferase 3A opposite strandDnmt3aDNA methyltransferase 3aBMDMbone marrow-derived macrophagesMeDIP-seqmethylated DNA immunoprecipitation sequencingLPSlipopolysaccharidesIFN-γinterferon-gammaGM-CSFgranulocyte-macrophage colony stimulating factorIL-4interleukin-4IL-12interleukin-12IL-13interleukin-13TNF-αtumor necrosis factor alphaNOnitric oxideCD80cluster of differentiation 80CD68cluster of differentiation 68M-CSFmacrophage colony stimulating factorsTGF-βtransforming growth factor beta-1Arg-1Arginase 1YM1chitinase 3-like 3Fizz1Resistin-like-αDMRdifferentially methylated regionUTRuntranslated regionCDScoding sequenceTTRtranscriptional termination regionGOgene ontologyDEGdifferentially expressed gene5-Aza-CdR5-Aza-2’-deoxycytidineBSPbisulfite sequencing PCRncRNAnon-coding RNA.