Research press release


Nature Methods

Never-ending supply of antibodies



小出 昌平(こいで・しょうへい)たちは動物による抗体生産に見切りをつけ、遺伝子ツールを利用することにより、ヒストン上の特定の修飾に対する特異性の高い組み換え抗体を細菌で作製した。その抗体は、動物を用いて生産された市販の抗体と比較して、性能が優れているとともに、時間が経っても質が劣化しないことが明らかにされた。また、その作製法では複数の修飾に対する抗体の開発も可能であり、それは例えば、隣接するメチル基やそのほかの後生的な修飾の組み合わせが遺伝子発現に対してどのように影響するのかを明らかにするうえできわめて有用と考えられる。

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.

doi: 10.1038/nmeth.2605

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