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DNA methylation and chromatin modifications were once generally considered to be distinct mechanisms that were only grouped together based on their roles as epigenetic regulators. Many labs specialized in either chromatin or DNA methylation research.
While this approach certainly led to deeper technical expertise for studying each type of mark, mounting evidence suggests that these epigenetic mechanisms do not operate independently and often exhibit crosstalk (Fischle, 2008; Cedar & Bergman, 2009; Lee et al., 2010).
Several recent reports have indicated that there are substantial interactions between DNA methylation and chomatin modifications. However, those findings could only be derived from correlative studies or parallel experiments on various epigenetic marks, due to a lack of adequate techniques to allow simultaneous analysis of DNA methylation and chromatin modification.
In 2012, two groups, working separately, bridged that technology gap with unique approaches based on a combination of familiar epigenetic analysis protocols. The work was published in the same issue of Genome Research, and both applied chromatin immunoprecipitation (ChIP) and bisulfite sequencing (BS) together, but used them in a different sequence.
Each of the new methods combined the same basic tools to allow successful combinatorial profiling of DNA methylation and chromatin modifications at the same time.
Scientists at Radboud University in the Netherlands and the Broad Institute in Boston developed ChIP-BS-seq (Brinkman et al., 2012). This is a system where they bisulfite treat previously chromatin immunoprecipitated material and then sequence those samples.
Their approach allowed them to determine relationships between DNA methylation and chromatin features:
Researchers from the Garvan Institute for Medical Research in Australia, constructed their DNA methylation-chromatin crosstalk tool, BisChIP-seq, in the opposite way. This technique bisulfite treats the DNA first, then proceeds to ChIP and sequence samples (Statham et al., 2012).
Their BisChIP-seq assessment yielded several interesting results:
Both ChIP-BS-seq and BisChIP-seq offer a means to directly investigate the relationship between chromatin modifications and DNA methylation. This combinatorial analysis of chromatin and DNA methylation represents a big advancement from previous correlative studies and promises to provide a platform towards a deeper understanding of epigenetic mechanisms.