Mononuclear Phagocyte Biology
Epigenetics of Cell Differentiation

What's the impact of genome architecture on differentiation and function of myeloid cells?

The last few years have seen tremendous progress in our understanding of the mutational landscape in acute myeloid leukaemia (AML) with several genes involved in epigenetic (e.g. TET2, DNMT3A, etc.) or architectural control of transcription processes (e.g. cohesin members STAG2, SMC3, SMC1A, and RAD21) being recurrently mutated. However, we are still far from understanding the complex networks that control leukaemogenesis. While epigenetic changes are well documented and have received much attention in the last decade, these data are usually in a linear spatial context and ignore the three-dimensional organization of chromatin in the nucleus, which is likely altered during leukemic transformation. In this project, we will try to understand the relationship between three-dimensional chromatin organization, and (epi-)genomic alterations during myelopoiesis and leukemic transformation.

scheme

On the one hand, we are studying the impact of cohesin-depletion in post-mitotic monocytes, which enables us to focus on transcriptional effects. On the other hand, we investigate effects of cohesin loss in differentiating hematopoietic stem or leukemia cells.


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Michael Rehli • Dept. Internal Medicine III • University Hospital
F.-J.-Strauss Allee 11 • 93053 Regensburg • Germany

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