Never-ending supply of antibodies

A strategy to make renewable, high quality reagents to study how the genome is regulated is reported in a paper published online this week in Nature Methods. The method addresses the ‘antibody bottleneck’: the fact that current antibodies used to identify proteins that turn gene expression on or off are not renewable and often do not specifically recognize their intended target.

Gene expression is regulated not only by the four bases that make up the DNA, but also by proteins that are associated with the DNA, especially histones (the protein ‘spools’ that the DNA is wound around). Chemical modifications of these histones, for example the addition of a methyl group at a certain amino acid, influence whether a gene encoded in the DNA is expressed or not. Researchers rely heavily on antibodies that recognize specific modifications on these histones to understand their impact on genome regulation. The challenge is that these antibodies are mostly generated in animals in distinct batches with large variations in quality from batch to batch. Once a good batch runs out, there is no guarantee that the next batch will perform equally well.

Shohei Koide and colleagues cease antibody production in animals and instead use genetic tools to make recombinant antibodies in bacteria with high specificity for certain modifications on histones. Comparing their tools to commercial antibodies produced in animals the researchers show better performance and no decline in quality over time. Their production method also permits developing antibodies to more than one modification which will be very useful in deciphering, for example, how adjacent methyl groups or other combinations of epigenetic modifications influence gene expression.