Sequencing: Probing epigenetic cross-talk

  • Tal Nawy
  • Published 2012 in Nature Methods


538 | VOL.9 NO.6 | JUNE 2012 | nature methods Both groups used the technique to study the cross-talk between trimethylation of lysine 27 on histone 3 (H3K27me3) and DNA methylation. The two marks have been suggested to be mutually exclusive in regulatory regions that include a dense representation of the sequence ‘CG’ (termed CpG islands). One theory posits that DNA methylation is a more permanent mark that replaces H3K27me3 during the differentiation of stem cells. Results from the Stunnenberg group corroborated this antagonism, whereas the Clark study found both unmethylated and highly methylated DNA in CpG islands, depending on genomic location—which suggests that independent mechanisms lay down the two marks. The different cell lines used may account for these divergent findings; the researchers are investigating the cause. Sequential bisulfite sequencing can be used with any method that enriches target DNA, and as Clark’s group showed, the results are strand-specific, providing allelic resolution. The Stunnenberg group has used the method to determine whether selective protein ‘readers’ of methylated DNA discovered with in vitro tools actually bind methylated DNA in vivo. “We need to have absolute certainty that we’re looking at DNA of the same strand on which we have done the ChIP,” Stunnenberg says. They are finding that even well-established methylated-DNA binding proteins may not hold up to in vivo scrutiny. Stunnenberg is captivated with the potential for sequential ChIP and bisulfite sequencing to investigate allele-specific effects and imprinting in epigenetic phenomen. Clark wants to investigate other histone marks and genome-binding factors to understand their direct relationship to the DNA methylome. More meaningful maps relating DNA methylation to chromatin are sure to come. tal nawy

DOI: 10.1038/nmeth.2063

Cite this paper

@article{Nawy2012SequencingPE, title={Sequencing: Probing epigenetic cross-talk}, author={Tal Nawy}, journal={Nature Methods}, year={2012}, volume={9}, pages={538-538} }