LncRNA Mediated Human Genomic DNA Methylation

DNA methylation is a key epigenetic modification in mammals which associated with transcriptional regulation, cell differentiation and embryonic development. The widely-reported that DNA methylation is catalyzed by a family of DNA methyltransferase(Dnmts) which include Dnmt1,Dnmt3 a and Dnmt3 b,those transfer a methyl from S-adenyl methionine(SAM) to the fifth C of cytosine. Expect that some studies show that the de novo DNA methyltransferase 3-like(Dnmt3L) is a catalytically inactive DNA methyltransferase which cooperates with Dnmt3 a and Dnmt3 b then activating the DNA methyltransferase. Many studies have showed that cytosine methylation is predominantly found in Cp G dinucleotide in mammals, but others have revealed that the DNA methylation was found in non-Cp G sites. Unlike that in mammals scientists have revealed the DNA methylation in plants generally happened in GC, CHG or CHH sits, except that the repeat elements and gene-coding regions were heavily methylated, but that in promoters almost non methylation. In the past few years research of DNA methylation in plants and mouse found the si RNA and lnc RNA interact with Dnmts to regulate the DNA methylation. End till this article there have not reported the DNA methylation could regulated by lnc RNA.In order to explore the mechanism of lnc RNA regulated human genomic DNA methylation, we get the nc RNA by RNA immune coprecipitation during Induction of Neural Pluripotent Stem Cells from Esc, then distinguish the lnc RNA from extraction.In this study, we can draw the following conclusions:1? The expression of Dnmt3 a and Dnmt3 b in the differentiation of ES cells to NPC cells is dynamic. And to participate in DNMT3 b positioning to some nc RNA on the genome, including three lnc RNA and other dozens of micro RNA, and found in the RNA and genomic binding sites in the vicinity found no phenomenon of DNA methylation.2? In ES cells, lnc RNA and micro RNA are able to bind to Dnmt3 b and mediate Dnmt3 b binding to the genome, and sno RNA is also involved in the process of ES cell differentiation. Therefore, we confirmed that lnc RNA was able to participate in the process of Dnmt3 b localization to the specific location of the genome in the process of human cell differentiation.3? During the differentiationof H9- ES cells to NPC cells, Dnmt3 a and Dnmt3 b expression quantity in the process of dynamic process, both at the time of differentiation on the second day express quantity highest, and the expression of Dnmt3 b quantity is higher than the number of Dnmt3 a expression4? During the differentiationof H9- ES cells to NPC cells, its binding sites nearby genes have 25 m RNA, 7 sno RNA, 2 micro RNA,1 lnc RNA. And we found that the RNA binding sites nearby genes methylation is higher, the binding sites present a high Cp G methylation phenomenon, and the main function of these genes are associated with cell differentiation and neural differentiation;5? In NPC cells we have found and Dnmt3 b combination of RNA, the binding sites nearby genes has 132 m RNA, 16 sno RNA, 5 micro RNA and 2 lnc RNA. By UCSC, we found that these can and Dnmt3 b RNA levels of DNA methylation in all nearby genes than high undifferentiated ES cells, and the Cp G methylation in these binding sites is also high. And its binding site near the function of the gene are related and RNA biosynthesis and degradation.