R-loop Formation is a Distinctive Characteristic of Unmethylated Human CpG Island Promoters

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2012 Mar 6

PMID 22387027

Citations 487

Authors

Paul A Ginno

Paul L Lott

Holly C Christensen

Ian Korf

Frederic Chedin

Affiliations

Soon will be listed here.

Abstract

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 cotranscriptional formation of R loop structures.

Citing Articles

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