Becker Group

We analyse the function of histone demethylases of the KDM6 family, which counteract the function of proteins of the Polycomb group. Our results to date show that inhibition of KDM6 in differentiating embryonic stem cells leads to a DNA damage response. Our work suggests that KDM6 demethylases are involved in maintaining genomic stability in addition to their role in regulating gene transcription. More recent research on the function of the KDM6 paralog KDM6A shows that KDM6A plays an important role in the function of haematopoietic stem and progenitor cells. We have now expanded our analyses to investigate the function of KDM6 demethylases in the adult heart and in response to ischaemic infarction.

Another important aspect of our work is the elucidation of epigenetic mechanisms during the differentiation of embryonic stem cells (ESCs). In this context, we analyse the role of non-coding RNA, such as microRNA-26 (miR-26) and long non-coding RNA (lncRNA) Malat1, during neural ESC differentiation. Our results show that miR-26 is an important factor at the beginning of neural differentiation. Furthermore, they reveal a previously unknown connection between Malat1 and miR-26 during the differentiation of neural precursor cells, thus providing unexpected insights into the ribo-regulation of neurogenesis.

Recent work has focused on the role of chromatin regulators such as TRIM28 and BCOR in the development of juvenile tumours such as Wilms' tumour, renal clear cell carcinoma and high-grade neuroepithelial tumours.  The aim is to understand the function of these factors in normal renal and neural development in order to gain new insights into their role in tumour development.