Action at a distance
While the textbook enhancer is often depicted just upstream of a gene, many enhancers influence transcription from afar—some can activate genes a million base pairs away. Enhancers can even activate genes on a completely separate chromosome (i.e., in trans), a process called transvection. It’s not known how common transvection is, but an article in the May issue of GENETICS suggests the phenomenon might occur more frequently than expected.
The researchers investigated multiple enhancers in the fruit fly Drosophila melanogaster. Although interactions between enhancers and genes in trans also occur in other organisms, the fruit fly is uniquely suited to the study of transvection. In Drosophila, homologous chromosomes pair not only in germ cells, but in somatic cells, increasing opportunities for interactions between the conjoined chromosomes. This makes it more likely that transvection can be observed.
To test the ability of any particular enhancer to activate transcription on another chromosome, the researchers developed expression reporters that could measure the strength of cis and trans activation at the same time. On one of the fly’s chromosomes, the researchers integrated an enhancer sequence followed by a promoter and the reporter gene lacZ. At the same site on the homologous chromosome, they omitted the enhancer, integrating only a promoter and a gene encoding green fluorescent protein (GFP). Because the enhancer and the GFP gene lie on separate chromosomes, if the enhancer can’t act in trans, there should be minimal GFP transcription. But if the enhancer can affect transcription on another chromosome, the transgenic fly cells should radiate a vibrant green color.
Unexpectedly, every one of the enhancers the researchers investigated was capable of producing green fluorescence in cells, indicating that all of them could act in trans, at least in the right circumstances. But some enhancers activated in trans much better than others. The team noticed the enhancers that produced the strongest GFP fluorescence also had the most transcription of lacZ, the gene cis to the enhancer.
This correlation explains much of the variance the researchers observed, but it isn’t the only factor that affects the robustness of transvection. For instance, the researchers also observed stronger transvection in specific cell types. Although we don’t yet know all the factors that affect transvection efficiency, this work reveals the surprising extent to which enhancers can impose their authority beyond the chromosome on which they reside.
Blick, A.J., Mayer-Hirshfeld, I., Malibiran, B.R., Cooper, M.A., Martino, P.A., Johnson, J.E., Bateman, J.R. (2016). The Capacity to Act in Trans Varies Among Drosophila Enhancers.