Differentiation-associated, macrophage-specific gene expression: Mechanisms of transcription regulation

• Applicant: Professor Dr. Michael Rehli
• Subject Area: Immunology ; Hematology, Oncology
• Term: from 2016 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 281585915

Differentiation of human monocytes into mature effector cells provides a unique model to study transcription regulation in the natural absence of proliferation. In addition, these cells display remarkable phenotypic plasticity enabling them to mature into phenotypically diverse cells like macrophages, dendritic cells or osteoclasts. This project aims at understanding transcriptional mechanisms controlling the differentiation of human monocytes. During the past funding period we have started to globally assess the dynamics of differentiation-associated transcription factor binding, chromatin remodeling and epigenetic changes to deduce key regulators of the monocyte to macrophage differentiation process. We particularly focused on the biology of enhancers, which are key to cell-type specific gene regulation. We would now like to continue this work and thoroughly characterize the interplay between transcription factor binding, chromatin remodeling and epigenetic changes during in vitro differentiation. In particular, we will continue to study the role of several transcription factors (including AP1, E-box binding factors, etc.) during macrophage differentiation and functionally analyse the role of individual, relevant enhancer elements. In addition, we would like to extend our transcriptional promoter and enhancer activity analyses to various macrophage subtypes (both in vitro generated and in vivo subsets) to address macrophage plasticity and the impact of a local microenvironment on macrophage activation on the systems biology level. The project will generate valuable resources for the macrophage community, provide novel and clinically-relevant insights into the biology of this interesting cell type and address more general aspects of enhancer biology.

• DFG Programme: Research Grants