Building a Test for Epigenetic Noxae
2024
Fischer, Falk | Kugler, Josephine
The epigenetic machinery partakes in governance of gene transcription, nuclear architecture, and maintenance of DNA integrity and is thus involved in virtually all cellular processes. Chemicals may exert drastic effects on epigenetics and perturbed epigenetics have also been associated with many diseases. Yet, due to the lack of test systems and defined endpoints, investigation of epigenetic effects is currently not part of any risk assessment. To address this, we develop a reporter system to monitor variations in open but transcriptionally inactive (bivalent) chromatin levels, which have been linked to developmental processes and cancer development. The reporter is based on modified histone-reader proteins that bind to the epigenetic marks that constitute bivalent chromatin to produce a Förster-resonance-energy transfer (FRET) signal. This approach may provide a noninvasive, fluorescence readout of bivalent chromatin content in living cells. The reporter yields FRET signals measured with multiple methods and first experiments indicate that cells with putatively different contents of bivalent chromatin can be measured. Current endeavors are focused on optimizing the analysis/readout and calibrating the readout with data generated by classical approaches.
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