Unknown,Transcriptomics,Genomics,Proteomics

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The Senescent Methylome and its relationship with cancer, ageing, and germline genetic variation in humans (methylation experiment 1)

ABSTRACT: Cellular senescence is a stable arrest of proliferation and is considered a key component of processes associated with carcinogenesis and other ageing-related phenotypes. However, till now, biological markers that define senescence on a genome-wide scale have been limited. Here, we report a DNA methylomic analysis of actively dividing and deeply senescent normal human epithelial cells, identifying 3,852 senescence-associated differentially methylated positions (senDMPs). We find that this human senDMP signature is positively and significantly correlated with both cancer and ageing-associated methylomic dynamics. We also identify germline genetic variants, including those associated with the p16INK4A locus, that are associated with the presence of in vivo senDMP signatures. Importantly, we also demonstrate that the senDMP signature can be effectively reversed in a newly-developed protocol of transient cellular rejuvenation. The senDMP signature has significant potential for understanding some of the key (epi)genetic etiological factors that lead to cancer and age-related diseases in humans. Bisulphite converted DNA from the HMECs at early passage (EP), deep senescence (DS), deep senescence + p16 siRNA (DS+p16siRNA) at two different time points and FACS for cell cycle at EP were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

ORGANISM(S): Homo sapiens

SUBMITTER: Robert Lowe

PROVIDER: E-GEOD-56719 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Constituting the final growth phase during the lifecycle of maize (Zea Mays L.), leaf senescence plays an important biological role in grain yield in crops. We undertook proteomic and physiological analyses in inbred line Yu816 in order to unravel the underlying mechanisms of leaf senescence induced by preventing pollination. A total of 6,941 proteins were identified by Isobaric tags for Relative and Absolute Quantitation (iTRAQ) analysis. Proteomic analyses between pollinated (POL) and non-pollinated (NONPOL) plants indicated that 973 different proteins accumulated in NONPOL plants. The accumulated proteins were classified into various groups, including response to stimuli, cellular processes, cell death and metabolic processes using functional analysis. Furthermore, in accordance with the changes in these different accumulated proteins, analysis of changes in leaf total soluble sugars and starch content showed that the prevention of pollination can disturb endogenousplant hormone and sugar metabolism and lead to ROS bursts, protein degradation and photosystem breakdown, eventually resulting in leaf senescence. This represents the first attempt at global proteome profiling in response to induced leaf senescence by preventing pollination in maize, and provides a better understanding of the molecular mechanisms involved in induced leaf senescence.Constituting the final growth phase during the lifecycle of maize (Zea Mays L.), leaf senescence plays an important biological role in grain yield in crops. We undertook proteomic and physiological analyses in inbred line Yu816 in order to unravel the underlying mechanisms of leaf senescence induced by preventing pollination. A total of 6,941 proteins were identified by Isobaric tags for Relative and Absolute Quantitation (iTRAQ) analysis. Proteomic analyses between pollinated (POL) and non-pollinated (NONPOL) plants indicated that 973 different proteins accumulated in NONPOL plants. The accumulated proteins were classified into various groups, including response to stimuli, cellular processes, cell death and metabolic processes using functional analysis. Furthermore, in accordance with the changes in these different accumulated proteins, analysis of changes in leaf total soluble sugars and starch content showed that the prevention of pollination can disturb endogenousplant hormone and sugar metabolism and lead to ROS bursts, protein degradation and photosystem breakdown, eventually resulting in leaf senescence. This represents the first attempt at global proteome profiling in response to induced leaf senescence by preventing pollination in maize, and provides a better understanding of the molecular mechanisms involved in induced leaf senescence.

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The Senescent Methylome and its relationship with cancer, ageing, and germline genetic variation in humans (methylation experiment 1)

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