R-loop formation is a distinctive characteristic of unmethylated human CpG island promoters
By Paul Adrian Ginno, P. Lott, H. Christensen, Ian Korf, Frédéric Chedin. Molecules and Cells, 2012
820 citations recorded by the source corpus.
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 methylation-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 methyltransferase 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 co-transcriptional formation of R-loop structures.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/2e3eac3c72637c4d4f68f0a74d4329a50adcc0ab
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Citations in the corpus
- R-loops as cellular regulators and genomic threats (2019, methodology): “In DRIP-seq, nucleic acids are extracted from unfixed cells and gently fragmented using restriction enzymes.”
- R loops: from transcription byproducts to threats to genome stability. (2012, background): “It has been proposed that the displaced ssDNA in the R loop acts as a signal to recruit either the protective H3K4 trimethyl mark or the DNA demethylases complex (Ginno et al., 2012) (Figure 1F).”