Unknown,Transcriptomics,Genomics,Proteomics

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Mammalian cells acquire epigenetic hallmarks of human cancer during immortalization

ABSTRACT: Progression to malignancy requires cells to overcome senescence and switch to an immortal phenotype. Thus, exploring the genetic and epigenetic changes that occur during senescence/immortalization may help elucidate crucial events that lead to cell transformation. In the present study, we have globally profiled DNA methylation in relation to gene expression in primary, senescent and immortalized mouse embryonic fibroblasts. Primary, senescent and immortalized mouse fibroblasts obtained from three independent embryos. Compare immortalized versus primary and senescent versus primary cells.

ORGANISM(S): Mus musculus

SUBMITTER: Xiwei Wu

PROVIDER: E-GEOD-39034 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Mammalian cells acquire epigenetic hallmarks of human cancer during immortalization.

Tommasi Stella S Zheng Albert A Weninger Annette A Bates Steven E SE Li Xuejun Arthur XA Wu Xiwei X Hollstein Monica M Besaratinia Ahmad A

Nucleic acids research 20121111 1

Progression to malignancy requires that cells overcome senescence and switch to an immortal phenotype. Thus, exploring the genetic and epigenetic changes that occur during senescence/immortalization may help elucidate crucial events that lead to cell transformation. In the present study, we have globally profiled DNA methylation in relation to gene expression in primary, senescent and immortalized mouse embryonic fibroblasts. Using a high-resolution genome-wide mapping technique, followed by ext ...[more]

PMID: 23143272

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Project description:Progression to malignancy requires that cells overcome senescence and switch to an immortal phenotype. Thus, exploring the genetic and epigenetic changes that occur during senescence/immortalization may help elucidate crucial events that lead to cell transformation. In the present study, we have globally profiled DNA methylation in relation to gene expression in primary, senescent and immortalized mouse embryonic fibroblasts. Using a high-resolution genome-wide mapping technique, followed by extensive locus-specific validation assays, we have identified 24 CpG islands that display significantly higher levels of CpG methylation in immortalized cell lines as compared to primary murine fibroblasts. Several of these hypermethylated CpG islands are associated with genes involved in the MEK-ERK pathway, one of the most frequently disrupted pathways in cancer. Approximately half of the hypermethylated targets are developmental regulators, and bind to the repressive Polycomb group (PcG) proteins, often in the context of bivalent chromatin in mouse embryonic stem cells. Because PcG-associated aberrant DNA methylation is a hallmark of several human malignancies, our methylation data suggest that epigenetic reprogramming of pluripotency genes may initiate cell immortalization. Consistent with methylome alterations, global gene expression analysis reveals that the vast majority of genes dysregulated during cell immortalization belongs to gene families that converge into the MEK-ERK pathway. Additionally, several dysregulated members of the MAP kinase network show concomitant hypermethylation of CpG islands. Unlocking alternative epigenetic routes for cell immortalization will be paramount for understanding crucial events leading to cell transformation. Unlike genetic alterations, epigenetic changes are reversible events, and as such, can be amenable to pharmacological interventions, which makes them appealing targets for cancer therapy when genetic approaches prove inadequate.

Dataset Information

Mammalian cells acquire epigenetic hallmarks of human cancer during immortalization

Publications

Mammalian cells acquire epigenetic hallmarks of human cancer during immortalization.

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