MED16 negatively regulates erythropoiesis and myelopoiesis through modulation of chromatin accessibility [ChIP-Seq mouse]

The Mediator complex plays a crucial role in regulating gene expression by interacting with transcription factors. In this study, we investigated the function of MED16, a core member of the tail module of the Mediator complex, in hematopoietic development. Our findings reveal that MED16 serves as a critical modulator of hematopoiesis by controlling chromatin accessibility at specific target genes. Loss of MED16 leads to a shift towards erythropoiesis and myelopoiesis in both human and mouse models. We found that MED16 deficiency increases chromatin accessibility at the RUNX1-binding promoter, promoting the expression of erythroid and innate immunity genes through cooperation with the FAcilitate Chromatin Transcription (FACT) complex. Furthermore, our study suggests that high MED16 expression may serve as a potential biomarker for myelodysplastic syndromes (MDS). Knockdown of MED16 in bone marrow mononuclear cells (BMMNCs) of MDS promotes erythroid differentiation, which may offer a potential therapeutic strategy for hematopoietic dysplasia diseases. Our findings demonstrate that MED16 acts as a negative regulator of erythroid and myeloid development and demonstrate its critical role in modulating the chromatin landscape in cooperation with RUNX1 and the FACT complex. To investigate the MED16 in the regulation of erythroid differentiation, we established HSPCs in which MED16 has been been knocked down by shRNA. Chromatin immunoprecipitation DNA-sequencing(Chip-seq) for MED16,RUNX1,SPT16 in HSPCs/erythroblasts Colocalization analysis of Chip seq for MED16 and RUNX1 in HSPCs/erythroblasts. Comparative chromatin binding profiling analysis of MED16 and SPT16 in HSPCs/erythroblasts and it s KD derivatives.