Proteomics

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A quantitative proteomic based approach to study the genistein induced epigenetic reprogramming in MDA-MB231 cells


ABSTRACT: Epidemiological data indicate that consumption of soy-based food significantly reduces the cancer risk in human through interaction with estrogen receptors and the ‘phytoestrogen’ genistein present in the soy is responsible for this chemopreventive activity. The epigenome regulatory effect of genistein also reported but the key mechanism behind this effect remain elusive. In this current project, we reported the epigenome modulation effect of genistein using MDA-MB231 cells. Cells were treated with low-dose genistein for >1 month and the stable epigenetic alterations were analyzed by partial MNase digestion and TMT-based quantitative proteomics based chromatome mapping approach. We identified a total of 3177 chromatin-bound proteins with high confidence, including 882 proteins that displayed altered binding topology after cell conditioning with genistein. Prolonged phytochemical exposure permanently modified the binding topology of the key epigenetic regulators and preserved their binding topology in untreated progeny. Genistein induced altered epigenome modulation negatively regulates the expression of cell proliferation genes and suppress cell growth. In contrast, previously exposed cells displayed reduced expression of DNA repair genes and enhanced genotoxic stress upon genistein withdrawal.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Bamaprasad Dutta  

LAB HEAD: Siu Kwan Sze

PROVIDER: PXD006178 | Pride | 2018-07-05

REPOSITORIES: Pride

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Publications

Soy-Derived Phytochemical Genistein Modifies Chromatome Topology to Restrict Cancer Cell Proliferation.

Dutta Bamaprasad B   Park Jung Eun JE   Qing Ivan Toh Yi ITY   Kon Oi Lian OL   Sze Siu Kwan SK  

Proteomics 20180806 16


Epidemiological data indicate that human cancer risk is significantly reduced by the consumption of soy-based foods containing the "phytoestrogen" genistein, which can signal via host cell estrogen receptors. While additional chemoprotective effects of genistein induced by epigenetic factors have also been reported, the key molecules and mechanisms involved are poorly defined. We therefore investigated genistein effects on chromatin-bound proteins in the estrogen receptor-deficient cell line MDA  ...[more]

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