Histone methyltransferase DOT1L controls state-specific identity during B cell differentiation

ABSTRACT: Differentiation of naïve peripheral B cells into terminally differentiated plasma cells is characterized by epigenetic alterations, yet the epigenetic mechanisms that control B cell fate remain unclear. Here we identified a role for the histone H3K79 methyltransferase DOT1L in controlling B cell differentiation. Mouse B cells lacking Dot1L failed to establish germinal centers (GC) and normal humoral immune responses in vivo. In vitro, activated B cells in which Dot1L was deleted showed aberrant differentiation and prematurely acquired plasma cell characteristics. Similar results were obtained when DOT1L was chemically inhibited in mature B cells in vitro. Mechanistically, combined epigenomics and transcriptomics analysis revealed that DOT1L promotes expression of a pro-proliferative, pro-G

SUBMITTER: Muhammad, Assad Aslam 

PROVIDER: S-SCDT-EMBOR-2020-51184V1 | biostudies-other |

REPOSITORIES: biostudies-other