Mutant mice lacking alternatively spliced p53 isoforms unveil as a male-specific prognostic factor in Myc-driven B-cell lymphomas.

The gene encodes several isoforms of elusive biological significance. Here, we show that mice lacking the alternatively spliced (AS) exon, thereby expressing the canonical p53 protein but not isoforms with the AS C-terminus, have unexpectedly lost a male-specific protection against Myc-induced B-cell lymphomas. Lymphomagenesis was delayed in males compared to males, but also compared to and females.

A systematic approach identifies p53-DREAM pathway target genes associated with blood or brain abnormalities.

p53 (encoded by Trp53) is a tumor suppressor, but mouse models have revealed that increased p53 activity may cause bone marrow failure, likely through dimerization partner, RB-like, E2F4/E2F5 and MuvB (DREAM) complex-mediated gene repression. Here, we designed a systematic approach to identify p53-DREAM pathway targets, the repression of which might contribute to abnormal hematopoiesis. We used Gene Ontology analysis to study transcriptomic changes associated with bone marrow cell differentiation, then chromatin immunoprecipitation-sequencing (ChIP-seq) data to identify DREAM-bound promoters.