Transcription regulation

Gene transcription is regulated by a complex interplay of epigenetic modifications at cis-regulatory elements, transcription factor dynamics as well as the spatial organization of genomic regions into active or silenced nuclear subcompartments. We dissect structure-function relationships of regulatory chromatin interactions in different cellular systems and across scales from the molecular level transcription factor (TF) binding and nucleosome occupancy to the 0.1-1 µm mesoscale of nuclear subcompartments. This work includes the characterization of genome-wide transcriptional changes that are perturbed by external stimuli or deregulation in cancer but also study of cellular model systems that are amenable to site-directed perturbations. We integrate both quantitative fluorescence microscopy and multi-omics single cell sequencing readouts (scRNA-seq, scCUT&Tag-seq, scATAC-seq, scHiC-seq). By perturbing chromatin states with respect to the TF and co-activator binding or histone modifications we identify chromatin features that characterize distinct promoter and enhancer states as well as their regulatory interactions. In addition, we employ light-inducible designer transcription factors (TFs) and biophysical approaches (FRAP, FCS, super-resolution microscopy) to probe the organizational principles underlying both active and silenced chromatin compartments such as pericentric heterochromatin foci and evaluate the contribution of phase-separated transcriptional condensates to gene regulation.

Cell type specific interferon response. Gene induction via chromatin context-dependent STAT1/2 binding at promoters or enhancers can be facilitated or repressed via preexisting chromatin states marked by the indicated chromatin features that can differ between cell types.

Key references

Muckenhuber M, Seufert I, Müller-Ott K, Mallm JP, Klett LC, Knotz C, Hechler J, Kepper N, Erdel F, Rippe K (2023) Epigenetic signals that direct cell type specific interferon beta response in mouse cells. Life Sci Alliance 6, e202201823. doi: 10.26508/lsa.202201823 | Abstract | Reprint | Article metrics

Trojanowski J, Frank L, Rademacher A, Mücke N, Grigaitis P, Rippe K (2022) Transcription activation is enhanced by multivalent interactions independent of phase separation. Mol Cell 82, 1878-1893. doi: 10.1016/j.molcel.2022.04.017 | Abstract | Reprint | Article metrics

Rademacher A, Erdel F, Trojanowski J, Schumacher S & Rippe K (2017). Real-time observation of light-controlled transcription in living cells. J Cell Sci 130, 4213-4224. doi: 10.1242/jcs.205534 | Abstract | Reprint (12.9 MB) | JCS First person | Article metrics