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Molecular mechanisms of the Polycomb Repressive Complex 2 (PRC2)

Grafik: Sabrina Fischer

The polycomb repressive complex 2 (PRC2) plays fundamental roles during developmental processes and in many human diseases, such as cancer. PRC2 functions as a transcriptional repressor by depositing the repressive H3K27me3 mark. However, the precise function of PRC2 in physiological and patho-physiological contexts remains incompletely understood. Importantly, recent work identified novel interacting partners of PRC2, demonstrating the highly sophisticated regulation of PRC2.

The polycomb like proteins (PCLs), PHF1, MTF2 and PHF19 are multidomain proteins, which possess a Tudor domain, two PHD fingers, an winged-helix-like domain and chromo-like domain. We and others found that the Tudor domain specifically binds to the histone mark H3K36me3. Further, we identified the chromo-like domain as the domain that is necessary and sufficient for the interaction with PRC2. More recent work identified the wing-helix-like domain as a novel DNA binding domain that specifically interacts with unmethylated CpG-rich sequences, providing a direct link between PRC2 and its known localization at CpG islands. These functions together suggest that polycomb-like proteins play crucial roles for the recruitment of PRC2 to its gene targets.

Another protein, EPOP, is a mammalian specific interacting partner of PRC2, which negatively affects the chromatin binding of PRC2, thus acting as an inhibitor of PRC2 functions. Further works suggests that EPOP potentially also plays a role at active genes via its interaction with the transcription elongation factor Elongin BC and the deubiquitinase USP7.

Future work of my groups aims to further elucidate the roles of EPOP and the Polycomb-like proteins.

Role of PRC2 in human cancer
PRC2 is commonly miss-regulated in many cancer types. EPOP and the Polycomb-like proteins MTF2 and PHF19 are often upregulated in cancer, suggesting that they may be involved in tumorigenesis. My group aims to elucidate the role of these proteins in cancer and to interfere with their function by small molecules, which could potentially lead to novel drugs and treatment options for cancer patients.

Molecular Mechanisms of human Adipogenesis
Further, we started to investigate the differential gene regulatory mechanisms between human visceral and subcutaneous adipocytes. We aim to better understand how human adipogenesis can be influenced in order to treat obesity associated diseases, such as diabetes.

If you are interested to work in my lab as a PhD or Master student, please send an email with a CV to (German and English skills are expected).