Human senescence ChIP-seq

Mammalian aging is characterized by the progressive loss of tissue integrity and function manifesting in ill health and increased risk for developing multiple chronic conditions. Accumulation of senescent cells in aging tissues partly contributes to this decline as targeted depletion of senescent cells in vivo ameliorates many age-related phenotypes. However, the fundamental molecular mechanisms responsible for the decline of cellular health and fitness during senescence and aging are largely unknown. In this study, we investigated whether chromatin-mediated loss of transcriptional fidelity, known to contribute to fitness and survival in yeast and worms, also occurs during human cellular senescence and mouse aging. Our findings reveal that aberrant transcription initiation inside genes is widespread in senescence and aging. It co-occurs with changes in the chromatin landscape and formation of non-canonical transcription start sites. Interventions that alter spurious transcripts have dramatic consequences on cellular health primarily affecting intracellular signal transduction pathways. We propose that spurious transcription is a conserved hallmark of aging that promotes a noisy transcriptome and a degradation of coherent transcriptional networks. Overall design: Includes one replicate each of H3K79me1 and H3K79me2 from proliferating and replicative senescent IMR90 fibroblasts. Includes two replicates of H2A.z, H3K36me3, three replicates of histone subunit H3, and four replicates of input from the same cells in the same conditions. H2A.z replicates and H3K36me3 replicates were pooled after alignment in the analysis; H3 samples are matched to each of the H3 histone PTM chIPs while input is matched to the H2A.z chIP (see "Matching Background" characteristic).