Histone acetylation mediates epigenetic regulation of transcriptional reprogramming in insects during metamorphosis, wounding and infection

Abstract

BackgroundGene expression in eukaryotes is regulated by histone acetylation/deacetylation, an epigenetic process mediated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) whose opposing activities are tightly regulated. The acetylation of histones by HATs increases DNA accessibility and promotes gene expression, whereas the removal of acetyl groups by HDACs has the opposite effect.ResultsWe explored the role of HDACs and HATs in epigenetic reprogramming during metamorphosis, wounding and infection in the lepidopteran model host Galleria mellonella. We measured the expression of genes encoding components of HATs and HDACs to monitor the transcriptional activity of each enzyme complex and found that both enzymes were upregulated during pupation. Specific HAT inhibitors were able to postpone pupation and to reduce insect survival following wounding, whereas HDAC inhibitors accelerated pupation and increased survival. The administration of HDAC inhibitors modulated the expression of effector genes with key roles in tissue remodeling (matrix metalloproteinase), the regulation of sepsis (inhibitor of metalloproteinases from insects) and host defense (antimicrobial peptides), and simultaneously induced HAT activity, suggesting that histone acetylation is regulated by a feedback mechanism. We also discovered that both the entomopathogenic fungus Metarhizium anisopliae and the human bacterial pathogen Listeria monocytogenes can delay metamorphosis in G. mellonella by skewing the HDAC/HAT balance.ConclusionsOur study provides for the first evidence that pathogenic bacteria can interfere with the regulation of HDACs and HATs in insects which appear to manipulate host immunity and development. We conclude that histone acetylation/deacetylation in insects mediates transcriptional reprogramming during metamorphosis and in response to wounding and infection.

The maternal transfer of bacteria can mediate trans-generational immune priming in insects

“…14,30 The coincidence between immune suppression and delayed development during infections has recently been attributed to the ability of bacterial and fungal pathogens to interfere with host epigenetic mechanisms including histone acetylation, which plays an essential role in the regulation of transcriptional reprogramming. 31 To summarize, we have discovered an unexpectedly simple mechanism by which trans-generational immune priming can be achieved in insects. The translocation of ingested bacteria from the gut lumen into the hemocoel, and their subsequent deposition in the eggs, can plausibly explain the observed bacterial species-dependent effects on maternal fecundity and offspring immunity.…”

Seasonal phenotype‐specific transcriptional reprogramming during metamorphosis in the European map butterfly Araschnia levana

“…The upregulation of a methyltransferase under LD conditions suggests that the transcriptional reprogramming that accompanies seasonal polyphenism may be regulated by epigenetic mechanisms, as we recently confirmed in another lepidopteran species (Mukherjee et al. 2012; Mukherjee and Vilcinskas 2014). …”

Kaposi's Sarcoma-Associated Herpesvirus-Encoded LANA Contributes to Viral Latent Replication by Activating Phosphorylation of Survivin

“…Survivin regulates the activities of histone acetyltransferases and deacetylases in KSHV-infected B-lymphoma cells. Histone acetylation is regulated by a balance of opposing histone deacetylase (HDAC) and histone acetyltransferase (HAT) activities (71). HATs can transfer an acetyl group of acetyl coenzyme A (acetylCoA) to the lysine epsilon amino groups at the N-terminal tails of histones and play a crucial role in transcriptional regulation of genes (72).…”