R-Loop Formation Is A Distinctive Characteristic Of Unmethylated Human CpG Island Promoters

Drareg

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Feb 18, 2016
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This is interesting,to speculate as anger out as it may be it could be possible to create a supplement that encourages RLoops.

SUMMARY

CpG islands (CGIs) function as promoters for approximately 60% of human genes. Most of these elements remain protected from CpG methylation, a prevalent epigenetic modification associated with transcriptional silencing. Here, we report that methyl- ation-resistant CGI promoters are characterized by significant strand asymmetry in the distribution of guanines and cytosines (GC skew) immediately downstream from their transcription start sites. Using innovative genomics methodologies, we show that transcription through regions of GC skew leads to the formation of long R loop structures. Furthermore, we show that GC skew and R loop formation potential is correlated with and predictive of the unmethylated state of CGIs. Finally, we provide evidence that R loop formation protects from DNMT3B1, the primary de novo DNA methyltransfer- ase in early development. Altogether, these results suggest that protection from DNA methylation is a built-in characteristic of the DNA sequence of CGI promoters that is revealed by the cotranscriptional formation of R loop structures.
http://www.cell.com/molecular-cell/pdf/S1097-2765(12)00083-4.pdf
 
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