Researchers reprogram social behaviour in carpenter ants using epigenetic drugs.

Epigenetics is a process whereby environmental factors can affect DNA and the mechanism by which DNA is transcribed and translated into proteins. Epigenetic regulation has been observed to affect a variety of distinct traits in animals, including body size, aging, and behaviour. However, there is an enormous gap in knowledge about the epigenetic mechanisms that regulate social behaviour.  Now, a study from researchers led-by University of Pennsylvania has shown that social behaviour can be reprogrammed, indicating that an individual’s downstream epigenetic, not upstream genetic, makeup determines behaviour in ant colonies.  The team state that their findings demonstrate how downstream epigenetic changes can have lasting effects on behaviour.  The study is published in the journal Science.

Previous studies show colonies of ants have a structured workforce where individuals have specialized responsibilities, though how this caste-based system is regulated at the molecular level has not been fully understood.  It has been suggested that histone acetylation could create dramatic differences in gene expression between genetically identical individuals, contributing to the physical differences in body size and reproductive ability between ant castes.  Earlier studies from the team developed the first genome-wide epigenetic maps in ants. This revealed that epigenetic regulation is key to distinguishing majors as the ‘brawny’ soldiers of carpenter ant colonies, compared to minors, their smaller, ‘brainier’ sisters. Major ants have large heads and powerful mandibles that help to defeat enemies and process and transport large food items. Minor ants are much smaller, outnumber majors two to one, and assume the important responsibility of searching for food and recruiting other ants to help with the harvest. Compared to majors, these foraging minors have genes involved in brain development and neurotransmission that are over expressed.  The current study shows that caste-specific foraging behaviour can be directly altered, by changing the balance of epigenetic chemicals called acetyl groups attached to histone protein complexes, around which DNA strands are wrapped in a cell nucleus.

The current study investigated two social groups of Camponotus floridanus, or Florida carpenter ants; minor ants are smaller and tend to forage for food, while major ants, which are larger, act as brawny soldiers.  The lab state that, in particular, chemical modifications to histone H3 (H3K27ac) are known to increase the foraging behaviour of Camponotus floridanus.  To test the effects of H3K27ac, minor ants were fed a compound that increases acetylation of H3K27ac.  Results show that foraging and scouting for food was enhanced with increased histone acetylation near genes involved in neuronal activity, and that inhibiting the addition of acetyl groups led to decreased foraging activity.

Data findings show that, in contrast to the dramatic boost in foraging seen in minors, feeding mature major workers these inhibitors caused little to no increase in foraging.  However, the researchers observed that directly injecting a more potent compound, trichostatin A (TSA), into the brains of very young majors just before the establishment of molecular barriers in the brain that restrict behavioural plasticity, caused them to immediately increase foraging.  Additionally, the team state that a single treatment with these inhibitors was sufficient to induce and sustain minor-like foraging in the majors for up to 50 days. They go on to add that these results suggest that there is an ‘epigenetic window of vulnerability’ in young ant brains, which confers increased susceptibility to environmental manipulations, such as with histone-modifying inhibitors.

The lab stress that all of the genes known to be major epigenetic regulators in mammals are also present in ants, which makes ants a fantastic model for studying principles of epigenetic modulation of behaviour and even longevity, because queens have a much longer lifespan compared to the major and minor workers.  Travelling upstream, the researchers state that the important gene implicated in the current study is CBP, which is an epigenetic ‘writer’ enzyme that alters chromatin by adding acetyl groups to histones. CBP, or cyclic adenosine monophosphate response element–binding protein (CREB) binding protein, has already been implicated as a critical enzyme facilitating learning and memory in mice and is mutated in certain human cognitive disorders, notably Rubinstein-Taybi syndrome.

The team surmise that their data shows that behavioural plasticity can be manipulated in the ant C. floridanus by pharmacological and genetic tools that target chromatin regulatory enzymes to stimulate, inhibit, and reprogram behaviour. They go on to add that in light of the conserved role of CBP in learning and memory in both invertebrates and mammals, their study suggests that CBP-mediated histone acetylation may similarly facilitate the complex social interactions found in vertebrate species.  For the future, the researchers state that they are focused on precisely defining the epigenetic window of vulnerability and its key molecular features.  They go on to conclude that understanding the mechanisms of when and how this window is opened, how changes are sustained, and why the window closes as the major ant ages, may have profound implications for explaining human vulnerability to early life exposures.

Source: University of Pennsylvania School of Medicine


Epigenetic mechanisms involved in regulation of gene expression. Cytosine residues within DNA can be methylated, and lysine and arginine residues of histone proteins can be modified. Me = methylation, Ac = acetylation, P = phosphorylation, Ub = ubiquitination.
Epigenetic mechanisms involved in regulation of gene expression. Cytosine residues within DNA can be methylated, and lysine and arginine residues of histone proteins can be modified. Me = methylation, Ac = acetylation, P = phosphorylation, Ub = ubiquitination.



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