Genes up-regulated H3K9me3 mediated senescence in mouse.
Full description or abstract
SUVARness is a senescence-associated transcriptional signature derived from genes upregulated during therapy-induced senescence (TIS) in the Eµ-myc mouse lymphoma model. The signature was designed to represent the transcriptional opposite of senescence impairment caused by loss of the H3K9 methyltransferase Suv39h1, a key regulator of H3K9me3-dependent senescence. TIS-upregulated genes were initially identified from three independent mouse lymphomas (4146, 4936, and 5043), each profiled under native, 5-day adriamycin (ADR)-induced senescence, and ADR plus 4-hydroxytamoxifen (4-OHT) conditions (9 expression profiles in total). This TIS-upregulated gene set was subsequently evaluated by Gene Set Enrichment Analysis (GSEA) across mouse and human lymphoma datasets. The final core SUVARness signature consists of the 22 genes shared among the leading-edge subsets from these GSEA analyses, representing a conserved, proliferation-independent H3K9me3-mediated senescence program. Mouse genes were mapped to their human orthologs to generate a humanized signature that predicts favorable progression-free and overall survival in patients with diffuse large B-cell lymphoma (DLBCL).
Collection
M2: Curated CGP: Chemical and Genetic Perturbations
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