Project description:In order to understand the role of H3K79me2 and DOT1L during CNS development, we analysed neural stem cells after pharmacological inhibition of DOT1L (5 µM SGC0946). To identify target genes of DOT1L in the cortex, we determined the transcriptome of cortical progenitor cells derived from E14.5 NMRI mice after interference with DOT1L activity for three days in vitro (DIV3). Therefore, three independent experiments were performed (ctrl1 – inh1, ctrl2 – inh2, ctrl3 – inh3).
Project description:Cellular binary fate decisions require the progeny to silence genes associated with the alternative fate. The major subsets of alpha:beta T cells have been extensively studied as a model system for fate decisions. While the transcription factor RUNX3 is required for the initiation of Cd4 silencing in CD8 T cell progenitors, it is not required to maintain the silencing of Cd4 and other helper T lineage genes. The other runt domain containing protein, RUNX1, silences Cd4 in an earlier T cell progenitor, but this silencing is reversed whereas the gene silencing after RUNX3 expression is not reverse. Therefore, we hypothesized that RUNX3 and not RUNX1 recruits other factors that maintains the silencing of helper T lineage genes in CD8 T cells. To this end, we performed a proteomics screen of RUNX1 and RUNX3 to determine candidate silencing factors.
