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Model of CSIG, PCNA, and CCNA2 transcriptional regulation in growing and senescent cells. In growing cells, E2F1 transactivates its target genes, including CSIG. When cells undergo senescence, Rb binds to the CSIG/PCNA/CCNA2 promoters. Both the TAAC element and the E2F1 binding site are required for this association. Subsequently, heterochromatin forms at the CSIG/PCNA/CCNA2 promoters and irreversibly represses CSIG/PCNA/CCNA2 transcription.
