EPILOG (epigenetic long-term consequences of viral and bacterial infections) is a joint research initiative with participating scientists from the University Medical Center Hamburg Eppendorf (UKE), the University of Hamburg (UHH) and the Heinrich Pette Institute, Leibniz Institute for Experimental Virology (HPI). The individual research groups study pathological as well as physiological consequences of epigenetic alterations induced by viral and bacterial infections.
Epigenetic modifications (DNA methylation and post-translational histone modifications) play a fundamental role in the regulation of cellular gene expression. Depending on its epigenetic state, chromatin may adopt an open or closed conformation, thus allowing or preventing access of DNA-binding factors or the transcriptional machinery to the underlying DNA. Whereas the genetic information provided by regulatory sequence elements is largely fixed, dynamic changes of its epigenetic state allow a cell to dynamically alter its transcriptional output. In addition to their role in mediating short-term responses, a number of epigenetic marks can also be stably transmitted throughout cell divisions. These inheritable marks form the basis of cellular memory; they are of quintessential importance for the maintenance of cellular identity, but also convey a learning system that allows cells to adapt to their environment. For example, the acquisition of immunological memory by the innate system (a property termed ‘trained immunity’) is largely dependent of epigenetic imprinting. In addition to their physiological role, it is also becoming increasingly clear that deregulated epigenetic processes contribute to the development of severe disease, including cancer and auto inflammatory syndromes.
While it is well known that acute or chronic infection can substantially influence host cell transcription, the long-term impact of infections upon the cellular epigenome remain poorly understood. Given their inheritability, it is a particular intriguing possibility that infection-associated epigenetic changes may even alter host cell functions long after the initial infection has been cleared. Within EPILOG, researchers will thus use interdisciplinary and systemic high throughput approaches to study epigenetic, chromatin and transcriptional changes induced by various pathogens on a genome wide scale. The group aims at elucidating common as well as pathogen-specific strategies to modulate the host cell epigenome, with a particular emphasis on persistent chromatin changes which may modulate innate immune responses or contribute to the development of chronic disease.