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.
Highlights
Gene 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
We recently analyzed the G. mellonella transcriptome during metamorphosis and/or following challenge with bacterial lipopolysaccharide (LPS) and identified several differentially-expressed genes encoding components of HATs and HDACs [14]. This suggested that HATs and HDACs are intimately involved in the control of transcriptional remodeling during metamorphosis and infection, and may regulate the injury-induced expression of genes encoding products such as the antimicrobial peptide galiomycin [15], the inhibitor of metalloproteinases from insects (IMPI), which protects against sepsis [16,17], mitogen-activated protein (MAP) kinase, which is involved in immunity-related signaling, and a matrix metalloproteinase involved in tissue remodeling during metamorphosis and infections [18,19]
We used the well-established G. mellonella model system [6,7,8,9,10,11,12,13,14] to show that epigenetic reprogramming during insect metamorphosis, wound healing and infection is controlled by histone acetylation/deacetylation, which in turn is regulated by HATs and HDACs with opposing activities
Summary
Gene 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. We recently analyzed the G. mellonella transcriptome during metamorphosis and/or following challenge with bacterial lipopolysaccharide (LPS) and identified several differentially-expressed genes encoding components of HATs and HDACs [14] This suggested that HATs and HDACs are intimately involved in the control of transcriptional remodeling during metamorphosis and infection, and may regulate the injury-induced expression of genes encoding products such as the antimicrobial peptide galiomycin [15], the inhibitor of metalloproteinases from insects (IMPI), which protects against sepsis [16,17], mitogen-activated protein (MAP) kinase, which is involved in immunity-related signaling, and a matrix metalloproteinase involved in tissue remodeling during metamorphosis and infections [18,19]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
