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- W3148704996 abstract "SUMMARY Senescent cells play important physiological- and pathophysiological roles in tumor suppression, tissue regeneration, and aging. While select genetic and epigenetic elements crucial for senescence induction were identified, the dynamics, underlying epigenetic mechanisms, and regulatory networks defining senescence competence, induction and maintenance remain poorly understood, precluding a deliberate therapeutic manipulation of these dynamic processes. Here, we show, using dynamic analyses of transcriptome and epigenome profiles, that the epigenetic state of enhancers predetermines their sequential activation during senescence. We demonstrate that activator protein 1 (AP-1) ‘imprints’ the senescence enhancer landscape effectively regulating transcriptional activities pertinent to the timely execution of the senescence program. We define and validate a hierarchical transcription factor (TF) network model and demonstrate its effectiveness for the design of senescence reprogramming experiments. Together, our findings define the dynamic nature and organizational principles of gene-regulatory elements driving the senescence program and reveal promising inroads for therapeutic manipulation of senescent cells." @default.
- W3148704996 created "2021-04-13" @default.
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- W3148704996 date "2019-05-09" @default.
- W3148704996 modified "2023-10-17" @default.
- W3148704996 title "AP-1 Imprints a Reversible Transcriptional Program of Senescent Cells" @default.
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- W3148704996 doi "https://doi.org/10.1101/633594" @default.
- W3148704996 hasPublicationYear "2019" @default.
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