Journal
CELL CYCLE
Volume 9, Issue 23, Pages 4622-4626Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.9.23.14211
Keywords
Myc; lymphoma; TGF beta; senescence; polycomb
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Funding
- Deutsche Forschungsgemeinschaft [Transregio 17]
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Deregulated expression of Myc under the control of an immunoglobulin enhancer induces lymphoma formation in mice. The development of lymphomas is limited by TGF beta-dependent senescence and high levels of Myc expression are continuously required to antagonize senescence. The biological processes underlying senescence are not fully resolved. We report here a comprehensive analysis of TGF beta-dependent alterations in gene expression when the Myc transgene is switched off. Our data show that Myc-induced target genes are down-regulated in a TGF beta-independent manner. In contrast, TGF beta is required to upregulate a broad spectrum of genes that are characteristic for different T-cell lineages when Myc is turned off. The analysis reveals a significant overlap between these Myc-repressed genes with genes that are targets of polycomb repressive complexes in embryonic stem cells. Therefore, TGF beta-dependent senescence is associated with gene expression patterns indicative of abortive cellular differentiation along several lineages.
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