Analyzing two epigenetic marks (DNA methylation and histone modification) by one sequencing run
Epigenetic regulation is a complicated network involving DNA methylation, histone modification and non-coding RNAs, which all play in concert to control the epigenetic machinery. The cross talk between DNA methylation and histone modification is one of the most important interactions in establishing the epigenetic signature and was traditionally studied using correlative approaches.
However, two recent papers published back-to-back in Genome Research described a novel method which can interrogate this epigenetic relationship directly by coupling chromatin immunoprecipitation with bisulfite sequencing, thus allowing investigation of two epigenetic marks on the same genome.
One paper found that histone H3 trimethylation at lysine 27 (H3K27me3) and DNA methylation are compatible and overlapping throughout most of the genome, except at CpG islands, where these two marks are mutually exclusive. The other paper found that alleles with different methylation statuses can simultaneously be associated with the H3K27me3 modification, indicating that DNA methylation is independent of histone modification.
Clearly, more work is needed to further define the interaction between DNA methylation and histone modification. Nevertheless, this technology provides a valuable tool to simultaneously analyze different epigenetic marks for a better understanding of their interaction.
View Full Paper: http://genome.cshlp.org/content/22/6/1120.long
Statham AL, Robinson MD, Song JZ, Coolen MW, Stirzaker C, Clark SJ. (2012) Bisulfite sequencing of chromatin immunoprecipitated DNA (BisChIP-seq) directly informs methylation status of histone-modified DNA. Genome Res. (6) 1120-7.
View Full Paper: http://genome.cshlp.org/content/22/6/1128.long
Brinkman AB, Gu H, Bartels SJ, Zhang Y, Matarese F, Simmer F, Marks H, Bock C, Gnirke A, Meissner A, Stunnenberg HG. (2012) Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk. Genome Res. (6) 1128-38.