Histone H2A deubiquitinase MYSM1 is essential for dendritic cell development (P4488)

Abstract

The mechanisms controlling differentiation of dendritic cells remain largely unknown. Using knockout mouse model, we identified Mysm1 as a critical regulator in dendritic cell differentiation. Mysm1 knockout mice showed a global reduction of both conventional dendritic cells and plasmacytoid dendritic cells in lymphoid organs and non-lymphoid organs whereas development of granulocyte and macrophage was not severely affected. Hematopoietic progenitors and dendritic cell precursors were significantly decreased in KO mice, and the precursor cells from Mysm1 knockout mice were unable to develop DC upon Flt3L stimulation in vitro. The developmental defect of Mysm1-/- progenitor cells was associated with decreased Flt3 expression. Molecular studies indicate that Mysm1 de-represses transcription of Flt3 gene by regulating histone modifications and mediating the recruitment of transcription factor Pu.1 at the promoter. In conclusion, we have identified a regulator of dendritic cell development, Mysm1, and provided novel mechanism of epigenetic control in steady-state dendritic cell development.