Project description: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.
Project description:To annotate estrogen-regulated eRNAs in MCF-7 breast cancer cells, we used precision nuclear run-on and sequencing of capped RNA (PRO-cap) to determine the transcription start sites of eRNAs.
Project description:Mapping of active transcription start sites using PRO-cap in whole-embryo at 3-4h and 6-8h AEL. Two biological replicates were performed at each time point.
Project description:Male Sirt7 KO mice exhibit an lifespan extension and increased FGF21 expression in liver. To reveal the mechanism of the increase of hepatic FGF21 expression in aged male Sirt7 KO mice, we performed RNA-seq analysis of the liver.
Project description:CoPRO experiment. A run-on assay was performed on captured nascent RNA with cap state selection. In this experiment, only uncapped nascent RNA was selected and no PCR amplification was done. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
Project description:CoPRO experiment. A run-on assay was performed on captured nascent RNA with cap state selection. In this experiment, only capped nascent RNA was selected and no PCR amplification was done. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
