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Stilbenoid-Mediated Epigenetic Activation of Semaphorin 3A in Breast Cancer Cells Involves Changes in Dynamic Interactions of DNA with DNMT3A and NF1C Transcription Factor

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Stilbenoid-Mediated Epigenetic Activation of Semaphorin 3A in Breast Cancer Cells Involves Changes in Dynamic Interactions of DNA with DNMT3A and NF1C Transcription Factor. / Beetch, Megan; Lubecka, Katarzyna; Shen, Kate; Flower, Kirsty; Harandi-Zadeh, Sadaf; Suderman, Matthew; Flanagan, James M.; Stefanska, Barbara.

In: Molecular Nutrition and Food Research, Vol. 63, No. 19, 1801386, 01.10.2019.

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Beetch, M, Lubecka, K, Shen, K, Flower, K, Harandi-Zadeh, S, Suderman, M, Flanagan, JM & Stefanska, B 2019, 'Stilbenoid-Mediated Epigenetic Activation of Semaphorin 3A in Breast Cancer Cells Involves Changes in Dynamic Interactions of DNA with DNMT3A and NF1C Transcription Factor', Molecular Nutrition and Food Research, vol. 63, no. 19, 1801386. https://doi.org/10.1002/mnfr.201801386

APA

Beetch, M., Lubecka, K., Shen, K., Flower, K., Harandi-Zadeh, S., Suderman, M., ... Stefanska, B. (2019). Stilbenoid-Mediated Epigenetic Activation of Semaphorin 3A in Breast Cancer Cells Involves Changes in Dynamic Interactions of DNA with DNMT3A and NF1C Transcription Factor. Molecular Nutrition and Food Research, 63(19), [1801386]. https://doi.org/10.1002/mnfr.201801386

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Author

Beetch, Megan ; Lubecka, Katarzyna ; Shen, Kate ; Flower, Kirsty ; Harandi-Zadeh, Sadaf ; Suderman, Matthew ; Flanagan, James M. ; Stefanska, Barbara. / Stilbenoid-Mediated Epigenetic Activation of Semaphorin 3A in Breast Cancer Cells Involves Changes in Dynamic Interactions of DNA with DNMT3A and NF1C Transcription Factor. In: Molecular Nutrition and Food Research. 2019 ; Vol. 63, No. 19.

Bibtex

@article{491152a15db64e2fa7d55c3a750902c9,
title = "Stilbenoid-Mediated Epigenetic Activation of Semaphorin 3A in Breast Cancer Cells Involves Changes in Dynamic Interactions of DNA with DNMT3A and NF1C Transcription Factor",
abstract = "SCOPE: Loci-specific increase in DNA methylation occurs in cancer and may underlie gene silencing. We investigate whether dietary stilbenoids, resveratrol and pterostilbene, exert time-dependent effects on DNA methylation patterns and specifically methylation-silenced tumor suppressor genes in breast cancer cells.METHODS AND RESULTS: Following genome-wide DNA methylation analysis with Illumina-450K, we identified changes characteristic of early and late response to stilbenoids. Interestingly, often the same genes but at different CpG loci, the same gene families or the same functional gene categories were affected. CpG loci that lost methylation in exposed cells corresponded to genes functionally associated with cancer suppression. There was a group of genes, including SEMA3A, at which the magnitude of hypomethylation in response to stilbenoids rises with increasing invasive potential of cancer cells. Decreased DNA methylation at SEMA3A promoter and concomitant gene upregulation coincided with increased occupancy of active histone marks. Open chromatin upon exposure to stilbenoids might be linked to decreased DNMT3A binding followed by increased NF1C transcription factor occupancy. Sequestration of DNMT3A is possibly a result of stilbenoid-mediated increase in SALL3 expression which was previously shown to bind and inhibit DNMT3A activity.CONCLUSIONS: Our findings define mechanistic players in stilbenoid-mediated epigenetic reactivation of genes suppressing cancer.",
keywords = "breast cancer, DNA methylation, DNMT3A, NF1C, stilbenoids, tumor suppression",
author = "Megan Beetch and Katarzyna Lubecka and Kate Shen and Kirsty Flower and Sadaf Harandi-Zadeh and Matthew Suderman and Flanagan, {James M.} and Barbara Stefanska",
year = "2019",
month = "10",
day = "1",
doi = "10.1002/mnfr.201801386",
language = "English",
volume = "63",
journal = "Molecular Nutrition and Food Research",
issn = "1613-4125",
publisher = "Wiley-VCH Verlag",
number = "19",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Stilbenoid-Mediated Epigenetic Activation of Semaphorin 3A in Breast Cancer Cells Involves Changes in Dynamic Interactions of DNA with DNMT3A and NF1C Transcription Factor

AU - Beetch, Megan

AU - Lubecka, Katarzyna

AU - Shen, Kate

AU - Flower, Kirsty

AU - Harandi-Zadeh, Sadaf

AU - Suderman, Matthew

AU - Flanagan, James M.

AU - Stefanska, Barbara

PY - 2019/10/1

Y1 - 2019/10/1

N2 - SCOPE: Loci-specific increase in DNA methylation occurs in cancer and may underlie gene silencing. We investigate whether dietary stilbenoids, resveratrol and pterostilbene, exert time-dependent effects on DNA methylation patterns and specifically methylation-silenced tumor suppressor genes in breast cancer cells.METHODS AND RESULTS: Following genome-wide DNA methylation analysis with Illumina-450K, we identified changes characteristic of early and late response to stilbenoids. Interestingly, often the same genes but at different CpG loci, the same gene families or the same functional gene categories were affected. CpG loci that lost methylation in exposed cells corresponded to genes functionally associated with cancer suppression. There was a group of genes, including SEMA3A, at which the magnitude of hypomethylation in response to stilbenoids rises with increasing invasive potential of cancer cells. Decreased DNA methylation at SEMA3A promoter and concomitant gene upregulation coincided with increased occupancy of active histone marks. Open chromatin upon exposure to stilbenoids might be linked to decreased DNMT3A binding followed by increased NF1C transcription factor occupancy. Sequestration of DNMT3A is possibly a result of stilbenoid-mediated increase in SALL3 expression which was previously shown to bind and inhibit DNMT3A activity.CONCLUSIONS: Our findings define mechanistic players in stilbenoid-mediated epigenetic reactivation of genes suppressing cancer.

AB - SCOPE: Loci-specific increase in DNA methylation occurs in cancer and may underlie gene silencing. We investigate whether dietary stilbenoids, resveratrol and pterostilbene, exert time-dependent effects on DNA methylation patterns and specifically methylation-silenced tumor suppressor genes in breast cancer cells.METHODS AND RESULTS: Following genome-wide DNA methylation analysis with Illumina-450K, we identified changes characteristic of early and late response to stilbenoids. Interestingly, often the same genes but at different CpG loci, the same gene families or the same functional gene categories were affected. CpG loci that lost methylation in exposed cells corresponded to genes functionally associated with cancer suppression. There was a group of genes, including SEMA3A, at which the magnitude of hypomethylation in response to stilbenoids rises with increasing invasive potential of cancer cells. Decreased DNA methylation at SEMA3A promoter and concomitant gene upregulation coincided with increased occupancy of active histone marks. Open chromatin upon exposure to stilbenoids might be linked to decreased DNMT3A binding followed by increased NF1C transcription factor occupancy. Sequestration of DNMT3A is possibly a result of stilbenoid-mediated increase in SALL3 expression which was previously shown to bind and inhibit DNMT3A activity.CONCLUSIONS: Our findings define mechanistic players in stilbenoid-mediated epigenetic reactivation of genes suppressing cancer.

KW - breast cancer

KW - DNA methylation

KW - DNMT3A

KW - NF1C

KW - stilbenoids

KW - tumor suppression

UR - http://www.scopus.com/inward/record.url?scp=85070111308&partnerID=8YFLogxK

U2 - 10.1002/mnfr.201801386

DO - 10.1002/mnfr.201801386

M3 - Article

C2 - 31327173

VL - 63

JO - Molecular Nutrition and Food Research

JF - Molecular Nutrition and Food Research

SN - 1613-4125

IS - 19

M1 - 1801386

ER -