PT  - JOURNAL ARTICLE
AU  - Muhammad Assad Aslam
AU  - Mir Farshid Alemdehy
AU  - Eliza Mari Kwesi-Maliepaard
AU  - Marieta Caganova
AU  - Iris N. Pardieck
AU  - Teun van den Brand
AU  - Fitriari Izzatunnisa Muhaimin
AU  - Tibor van Welsem
AU  - Iris de Rink
AU  - Ji-Ying Song
AU  - Elzo de Wit
AU  - Ramon Arens
AU  - Klaus Rajewsky
AU  - Heinz Jacobs
AU  - Fred van Leeuwen
TI  - Histone methyltransferase DOT1L controls state-specific identity during B cell differentiation
AID  - 10.1101/826370
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 826370
4099  - http://biorxiv.org/content/early/2019/11/18/826370.short
4100  - http://biorxiv.org/content/early/2019/11/18/826370.full
AB  - Development of naïve peripheral B cells into terminally differentiated plasma cells is a highly controlled process guided by epigenetic mechanisms. Here we identified a central role for the histone H3K79 methyltransferase DOT1L in controlling B cell development. Upon deletion of Dot1L early in the B-cell lineage, naïve and activated B cells prematurely acquired plasma cell features and failed to establish germinal centers (GC) and normal humoral immune responses in vivo. Transcriptome analyses revealed that DOT1L promotes expression of oncogenic, pro-proliferative and pro-GC transcription factors. Simultaneously, DOT1L indirectly promotes repression of anti-proliferative targets of the Polycomb Repressor Complex 2. Our findings show that DOT1L fine tunes the transcriptional and epigenetic landscape in B cells. In doing so it establishes a critical epigenetic barrier warranting B cell naivety and prohibiting their premature differentiation towards plasma cells.