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Long noncoding RNAs in DNA methylation: new players stepping into the old game.

Zhao Y, Sun H, Wang H - Cell Biosci (2016)

Bottom Line: Long non-coding RNAs (lncRNAs) are being discovered as a novel family of regulators of gene expression at the epigenetic level.Emerging lines of evidence demonstrate that interplays between lncRNAs and DNA methylation machinery are an important layer of epigenetic regulation.Here in this mini-review we summarize the current findings in the field and focus particularly on the interactions mediated through direct physical association between lncRNAs and DNA methyltransferases (DNMTs).

View Article: PubMed Central - PubMed

Affiliation: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.

ABSTRACT
Long non-coding RNAs (lncRNAs) are being discovered as a novel family of regulators of gene expression at the epigenetic level. Emerging lines of evidence demonstrate that interplays between lncRNAs and DNA methylation machinery are an important layer of epigenetic regulation. Here in this mini-review we summarize the current findings in the field and focus particularly on the interactions mediated through direct physical association between lncRNAs and DNA methyltransferases (DNMTs).

No MeSH data available.


The regulatory mechanisms of DNA methylation by lncRNAs. a lncRNA/DNMT1 interaction prevents locus-specific DNA methylation locally in cis (for example, ecCEBP). b lncRNA/DNMT1 interaction modulates DNA-methylation at distant genomic loci in trans, which may also require DNMT1-associated transcription factors (TFs) (for example, Dali). c lncRNA interacts with all three DNMTs (DNMT1, DNMT3a and 3b) to mediate/maintain local DNA methylation at the target promoter (for example, Dum). d lncRNA interacts with DNMT1 indirectly through a protein intermediate (for example, lincRNA-p21)
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Fig2: The regulatory mechanisms of DNA methylation by lncRNAs. a lncRNA/DNMT1 interaction prevents locus-specific DNA methylation locally in cis (for example, ecCEBP). b lncRNA/DNMT1 interaction modulates DNA-methylation at distant genomic loci in trans, which may also require DNMT1-associated transcription factors (TFs) (for example, Dali). c lncRNA interacts with all three DNMTs (DNMT1, DNMT3a and 3b) to mediate/maintain local DNA methylation at the target promoter (for example, Dum). d lncRNA interacts with DNMT1 indirectly through a protein intermediate (for example, lincRNA-p21)

Mentions: In conclusion, as modeled in Fig. 2, lncRNAs can modulate the DNA methylation through interacting with diverse DNMT members directly or indirectly. Through the action of recruitment or eviction they may either promote or repress DNA methylation in cis or in trans. The dynamic nature of lncRNA repertoire as well as the RNA plasticity in interacting with diverse molecules such as DNA, RNA and protein renders lncRNA an ideal mediator to regulate local and sequence-specific DNA methylation or demethylation, hence resulting in global changes in DNA methylation profile, through which cells can respond to diverse stimuli. In the future we anticipate that many other lncRNAs will be discovered to be involved in DNA methylation control. The dysregulation of these lncRNAs may trigger epigenetic disorders in various human diseases. Therefore, the future efforts in studying the regulatory roles of lncRNAs in epigenetic mechanisms will open new avenues for therapeutic targets for DNA methylation processes.Fig. 2


Long noncoding RNAs in DNA methylation: new players stepping into the old game.

Zhao Y, Sun H, Wang H - Cell Biosci (2016)

The regulatory mechanisms of DNA methylation by lncRNAs. a lncRNA/DNMT1 interaction prevents locus-specific DNA methylation locally in cis (for example, ecCEBP). b lncRNA/DNMT1 interaction modulates DNA-methylation at distant genomic loci in trans, which may also require DNMT1-associated transcription factors (TFs) (for example, Dali). c lncRNA interacts with all three DNMTs (DNMT1, DNMT3a and 3b) to mediate/maintain local DNA methylation at the target promoter (for example, Dum). d lncRNA interacts with DNMT1 indirectly through a protein intermediate (for example, lincRNA-p21)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4940868&req=5

Fig2: The regulatory mechanisms of DNA methylation by lncRNAs. a lncRNA/DNMT1 interaction prevents locus-specific DNA methylation locally in cis (for example, ecCEBP). b lncRNA/DNMT1 interaction modulates DNA-methylation at distant genomic loci in trans, which may also require DNMT1-associated transcription factors (TFs) (for example, Dali). c lncRNA interacts with all three DNMTs (DNMT1, DNMT3a and 3b) to mediate/maintain local DNA methylation at the target promoter (for example, Dum). d lncRNA interacts with DNMT1 indirectly through a protein intermediate (for example, lincRNA-p21)
Mentions: In conclusion, as modeled in Fig. 2, lncRNAs can modulate the DNA methylation through interacting with diverse DNMT members directly or indirectly. Through the action of recruitment or eviction they may either promote or repress DNA methylation in cis or in trans. The dynamic nature of lncRNA repertoire as well as the RNA plasticity in interacting with diverse molecules such as DNA, RNA and protein renders lncRNA an ideal mediator to regulate local and sequence-specific DNA methylation or demethylation, hence resulting in global changes in DNA methylation profile, through which cells can respond to diverse stimuli. In the future we anticipate that many other lncRNAs will be discovered to be involved in DNA methylation control. The dysregulation of these lncRNAs may trigger epigenetic disorders in various human diseases. Therefore, the future efforts in studying the regulatory roles of lncRNAs in epigenetic mechanisms will open new avenues for therapeutic targets for DNA methylation processes.Fig. 2

Bottom Line: Long non-coding RNAs (lncRNAs) are being discovered as a novel family of regulators of gene expression at the epigenetic level.Emerging lines of evidence demonstrate that interplays between lncRNAs and DNA methylation machinery are an important layer of epigenetic regulation.Here in this mini-review we summarize the current findings in the field and focus particularly on the interactions mediated through direct physical association between lncRNAs and DNA methyltransferases (DNMTs).

View Article: PubMed Central - PubMed

Affiliation: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.

ABSTRACT
Long non-coding RNAs (lncRNAs) are being discovered as a novel family of regulators of gene expression at the epigenetic level. Emerging lines of evidence demonstrate that interplays between lncRNAs and DNA methylation machinery are an important layer of epigenetic regulation. Here in this mini-review we summarize the current findings in the field and focus particularly on the interactions mediated through direct physical association between lncRNAs and DNA methyltransferases (DNMTs).

No MeSH data available.