Epigenetic regulation of myeloid cell differentiation

We have been studying the mechanism of myeloid cell development from the viewpoint of chromatin regulation by transcription factors. The transcription factor IRF8 is essential for the development of monocytes and dendritic cells (DCs), whereas it inhibits neutrophilic differentiation. We have demonstrated that IRF8 establishes enhancer landscapes in myeloid progenitors to epigenetically prime these cells to differentiate into monocytes or DCs. Recently, we focus on high-order chromatin structure during DC development. Our Hi-C data revealed that DC-specific active compartments are gradually established throughout the course of differentiation, while most of the topologically associating domains (TADs) specific for the DC lineage are formed with slower kinetics. We also found that the activation of DC-specific enhancers proceeds the compartment switch and subsequent gene expression. In addition, our data suggest that IRF8 is required for many of the DC-specific changes from compartment B to A. Collectively, myeloid cell gene expression patterns are epigenetically regulated by key transcription factors such as IRF8 via enhancer establishment and chromatin structure reorganization. Symposium 36