Modifications Abound

How to conduct your next large-scale epigenetic analysis

Aug 1, 2008
Jeffrey M. Perkel
<figcaption> Credit: Courtesy of Richard Young, Whitehead Institute for Biomedical Research, and Science</figcaption>
Credit: Courtesy of Richard Young, Whitehead Institute for Biomedical Research, and Science

Epigenetic changes are pivotal events in development and disease. With a constant genome, it is epigenetics - sequence-independent genetic control processes - that exert the molecular forces necessary to help cells remember their molecular heritage, turn somatic cells into stem cells, and forever silence Barr bodies in sex chromosome inactivation.

The National Institutes of Health acknowledged as much with its recently launched Roadmap Epigenomics Program, which seeks to map epigenetic modifications during normal development as a first step towards understanding how these processes can go awry. But how do you collect such data?

Epigenetics encompasses disparate control mechanisms that have little to do with DNA sequence per se. Methylcytosine often marks transcriptionally silent DNA. Histone tails studded with methyl, acetyl, and phosphate groups, among others, control how tightly DNA wraps around nucleosome spindles and how accessible that DNA is to protein binding. Noncoding RNA may be the genetic intermediary confining these elements to the genomic regions to which they belong.

One goal of the Epigenomics Program is to "develop new technologies for comprehensive epigenomic analyses." With decreasing microarray costs and the widening availability of next-generation sequencing platforms, researchers already have plenty of options for high-throughput epigenetic analysis. But each experimental solution will likely take some mixing and matching.

The Scientist asked five researchers about the techniques they use to collect epigenetic data on a genomic scale. Click on the user profiles in the yellow "Related Articles" box above to read what they said.