EpiTaG: Predicting Environmental Impacts on Future Generations by Delineating Causal Mechanisms of Transgenerational Epigenetic Inheritance

Human activities rapidly increase the burden of environmental stressors, like climate change or chemical exposures, leading to profound long-term impacts on humans and wildlife.

Increasing experimental evidence suggests that such impacts can be transferred to subsequent, unexposed generations by epigenetic processes.

Yet, while transgenerational epigenetic inheritance (TEI) is established on a descriptive level, the molecular mechanisms underlying TEI are largely unclear.

However, this is essential, not only for increasing our knowledge on TEI but also for predicting transgenerational impacts of environmental stressors.Using chemically exposed zebrafish as experimental paradigm, EpiTaG will:Generate novel insights into the epigenetic processes and their relationships underlying TEI, by developing an unprecedented high-resolution time course of DNA and RNA modifications and expression of non-coding RNA species, linked to genetic information and phenotypic transgenerational effects; Identify biomarkers predicting TEI by transformation of the epigenetic landscape to predictive key features using machine learning; andAddress, for the first time, causal involvement of identified biomarkers in TEI using (epi)genomic editing.This will lead to ground breaking new insights shifting transgenerational epigenetic inheritance from a descriptive to a functional mechanistic level and identify key features to predict, and thus potentially prevent, environmental impacts on future generations.