“All work and no play” is the norm for carpenter ants, where epigenetically distinct workers spend their days toiling away for their genetically identical colony-mates. The two classes of worker ants, minor workers who forage for food and major workers who protect the colony, differ in their size and appearance, but new research suggests that an epigenetic spark might be able to ignite a proletariat role-reversal.
Previously, the revolutionary researchers in Shelley Berger’s Lab (University of Pennsylvania, USA) found that they could induce foraging behavior in the major workers, who normally leave that task up to the minors, by injecting them with the HDAC inhibitor trichostatin A (TSA). Now, in a new study, they fine-tuned the timing of their technique and used it to understand the molecules behind the priority shift.
The talented team performed RNA-seq on the whole brains of individuals worker ants as they naturally developed into minors or majors as well as majors that were reprogrammed using TSA and found that:
- The expression of neuronal and chromatin-remodelling genes changes most drastically in the first 5 days of adulthood, in both classes of workers
- The number of genes that are differentially expressed between majors and minors decreases from 2500 in the first day of adulthood, to only 2 genes by day 10.
- Caste-specific genes include regulators of juvenile hormone (JH), which is expressed in minor workers and normally promotes foraging behavior
- The reprogramming of major workers has the strongest effect on the transcriptome 1 hour after TSA injection, and genes that are induced overlap with genes that are normally specific to minor workers
- H3K27ac, measured with ChIPseq, is enriched at the promoters of upregulated genes
Genes that are specific to TSA reprogramming are related to transcriptional repression and chromatin deactivation, including HDAC1 and the corepressor for element-1-silencing transcription factor (CoREST). Next, to understand how the molecule manages to manipulate behavior, the savvy scientists developed an antibody for CoREST, designed a ChIP-seq experiment, and found that:
- CoREST is enriched at the promoters of genes that are supressed by TSA reprogramming
- CoREST peaks are enriched for binding sites of other transcriptional repressors that are induced by reprogramming and normally supress major-associated gene programs
- Reprogramming decreases the expression of genes that degrade JH, increases the levels of CoREST at their promoters, and increases the amount of JH found in the ant brain via liquid chromatography-mass spectrometry (LC/MS)
- Genes that are normally expressed in minor workers have high levels of CoREST binding in normal major workers
In a final set of experiments, the researchers knocked down CoREST in major workers, using double stranded RNA, before TSA reprogramming, and found that CoREST is necessary for the successful job transfer. It turns out that CoREST pulls more than its fair share of the epigenetic workload in ant behavior.
The next step, according to Professor Berger is “…to understand which cell types in the brain are being individually regulated, since we have some interesting early data that this change in CoREST regulation is occurring in a very specific cell type in the brain.”
Clock-in and check out the details in Molecular Cell, January 2020.