BioProject

Upon activation, lymphocytes exit quiescence and undergo substantial increases in cell size and RNA content. More...

Upon activation, lymphocytes exit quiescence and undergo substantial increases in cell size and RNA content. A key regulator in this process is the Myc transcription factor, which is directly induced by activating signals and is required for multiple facets of cell activation, including metabolic reprogramming, chromatin decompaction, RNA and protein accumulation, cell growth and proliferation. However, how Myc activity impacts on those diverse cellular processes remains unclear. We addressed this issue in primary mouse B-cells, based on conditional deletion of the c-myc gene prior to LPS stimulation. Myc was rapidly induced, was recruited to virtually all active promoters and enhancers (a phenomenon known as invasion), but had no direct impact on global transcriptional activity. Instead, Myc contributed to the swift up- and down-regulation of several hundred genes, including many known regulators of the aforementioned cellular processes. Myc-activated promoters were enriched for E-box consensus motifs, bound Myc at the highest levels and showed enhanced RNA Polymerase II recruitment, the opposite being true at down-regulated loci. Remarkably, the Myc-dependent signature identified in activated B-cells was also enriched in Myc-driven B-cell lymphomas: hence, besides modulation of new cancer-specific programs, the oncogenic action of Myc may largely rely on sustained deregulation of its normal physiological targets. Overall design: Total RNA profiling of gene expression during LPS stimulation in primary wt or Myc-deleted (FLOX) B-cells Less...