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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.
This article was published in the following journal.
Name: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
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A basic leucine zipper transcription factor that regulates expression of MHC CLASS II GENES through its binding to a conserved X-box DNA sequence in the promoter region. It regulates the expression of genes involved in the UNFOLDED PROTEIN RESPONSE.
A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression.
A DNA (cytosine-5-)-methyltransferase that contains a central CxxC type zinc finger motif. It binds poly(ADP)-ribose and its expression is regulated by POLY (ADP-RIBOSE) POLYMERASE-1. DNMT1 methylates CpG residues, with a preference for hemimethylated DNA, and associates with DNA replication sites in S PHASE to maintain the methylation pattern in the newly synthesized strand, which is essential for EPIGENETIC PROCESSES. It also associates with CHROMATIN during G2 PHASE and MITOSIS to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development; mutations in the DNMT1 gene are associated with HEREDITARY SENSORY NEUROPATHY TYPE 1 class E.
A histone-lysine N-methyltransferase and catalytic subunit of Polycomb Repressive Complex 2. It methylates LYSINE 9 (H3K9me) and LYSINE 27 (H3K27me) of HISTONE H3, leading to transcriptional repression of the affected target gene. EZH2 also methylates non-histone proteins such as GATA4 TRANSCRIPTION FACTOR and the nuclear receptor RORA. It regulates CIRCADIAN CLOCKS via histone methylation at the PROMOTER REGIONS of the circadian genes and its repressive activity is also important for the identity and differentiation of EMBRYONIC STEM CELLS.
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