There are two sides to every story. Maybe even more if you ask a lawyer. So it only makes sense that two epigenetic mechanisms like chromatin and DNA methylation would each have something to say about the genomic regions they regulate. Two new methods each combine ChIP and bisulfite sequencing in order to cut through the noise and sort out Chromatin and DNA methylation crosstalk.
Even though they’re almost always studied separately, is becoming more and more clear that DNA methylation and Chromatin don’t just work in a vacuum, and in fact have important interactions. Two groups separately created new methods meant to analyze DNAm-Chromatin crosstalk through a combination of techniques familiar to most epigenetic labs; Chromatin immunoprecipitation (ChIP) and bisulfite treatment.
One team from Radboud University in the Netherlands and the Broad Institute developed a system where they sequentially ChIP, then bisulfite treat and sequence their samples, called ChIP-BS-Seq, that lets them see relationships between DNA methylation and Chromatin features. Here’s what ChIP-BS-Seq found:
- H3K27me3 and DNAm exist together in most of the genome, except for in CpG Islands.
- Embyonic stem (ES) cells without DNMT caused widespread H3K27me3 genomic changes, and broad local enrichments (BLOCs) popped up where DNA methylation used to be.
- DNA methylation appears to prevent H3K27me3
Another group, from the Garvan Institute for Medical Research in Australia ,built their own DNAm-Chromatin crosstalk tool using the same two protocols, but in a slightly different order. The Garvan team’s method, BisChIP-seq, bisulfite treats the DNA first, then ChIPs and sequences it. They dug up some interesting findings too, including:
- CpG islands and transcription start sites (TSS) of silenced genes in prostate cancer are enriched for both DNA methylation and H3K27me3 repressive marks
- There is less DNAm in intergenic regions with H3K27me3.
- Both methylated and unmethylated alleles can simultaneously associate with H3K27me3 histones, meaning that DNAm is not dependent on the polycomb chromatin status.
Both offer a direct approach to unravel the mysteries of chromatin and DNA methylation relationships, and represent a big step up from correlative studies, so give them a shot.
You can find these new methods in action at Genomics Research: