Epigenetic marks are like batman villains; they never seem to work alone. So why study them each alone? Recently, the trend in epigenetics has been studying multiple epigenetic marks simultaneously. This often saves time and money, but more importantly it gives better insight into what is actually going on in the cell.
Epigenetic marks function in a complex combinatorial code to affect gene expression (Ernst et al., 2011). Combinatorial epigenetic techniques have really evolved over the last few years, taking the best epigenetic techniques and combing them along with some clever data analysis. ChIP and bisulfite-seq have been combined to ChIP-BS-seq/BisChIP-seq. NoME-Seq uses de novo methylation to simultaneous examine nucleosome occupancy and CpG methylation. Finally CATCH-IT uses labeling of newly produced histones to unravel nucleosome dynamics.
Combinatorial Epigenetic Methods
ChIP-BS-seq and BisChIP-seq: These two similar approaches combine ChIP and bisulfite, two of the most informative epigenetic techniques.
NOMe-seq (Nucleosome Occupancy and Methylome Sequencing): Uses a de novo GpC methyltransferase and BS-seq to inform you about DNA methylation and nucleosome positions at the same time.
CATCH-IT (Covalent attachment of tags to capture histones and identify turnover): Is used to estimate the rates of assembly, disassembly or turnover of native nucleosomes.
Combinatorial Epigenetic Techniques Additional Reading
This text book chapter describes many examples showing how DNA methylation and histone modification are linked.
- Ernst, J., Kheradpour, P., Mikkelsen, T.S., Shoresh, N., Ward, L.D., Epstein, C.B., Zhang, X., Wang, L., Issner, R., Coyne, M., et al. (2011). Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 473, 43-49.