Investigating the role of SIRT1 in epigenetic effects of dietary phytoestrogens in human mammary epithelial cells
department or school: Land and Food Systems, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Ma, Yuexi
issued: 2025-04-30T07:00:00Z
issued: 2024
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Dietary factors, like polyphenols naturally occurring in plants, exert influences on human health via epigenetic mechanisms that alter gene expression without changing DNA sequence. We have previously performed genome-wide DNA methylation and expression analyses in human mammary epithelial cells and healthy rats’ livers, respectively, which were exposed to berry polyphenols with estrogenic activity (i.e., phytoestrogens). Using these datasets, we identified hypermethylated and/or downregulated genes enriched with functional categories that disrupt homeostasis and health maintenance, and promote aging, e.g., by limiting DNA break repair (RNF169) or promoting ribosomal biogenesis (rDNA). Existing evidence suggests that DNA methylation may be governed by chromatin regulatory proteins such as SIRT1 deacetylase. SIRT1 may interact with DNA methylating enzymes (e.g., DNMT3B) to repress transcription. Interestingly, SIRT1 was reported as a possible target of phytoestrogens. However, it remains unknown whether SIRT1 and its interaction with DNMT3B play a mechanistic role in phytoestrogen-mediated epigenetic effects in normal mammary epithelial cells. Thus, we test a hypothesis that phytoestrogens suppress genes related to homeostatic imbalance and aging, via SIRT1-mediated effects on DNA methylation. Human MCF10A mammary epithelial cells were treated with phytoestrogens, pterostilbene (PTS) and genistein (GEN). PTS and GEN decreased MCF10A cell growth with 50% inhibition and less than 10% dead cells at 11µM and 22µM concentrations respectively, as compared with vehicle-treated cells (control). SIRT1 occupancy at the selected hypermethylated phytoestrogen-target genes, RNF169 and rDNA, was accompanied by consistent promoter hypermethylation and gene downregulation in response to GEN, but not PTS. GEN-mediated DNA hypermethylation and SIRT1 occupancy were linked to a robust DNMT3B binding at both RNF169 and rDNA promoters. This was not observed in cells exposed to PTS, sugges…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/87884
note: Investigating the Role of SIRT1 in Epigenetic Effects of Dietary Phytoestrogens in Human Mammary Epithelial Cells by Yuexi Ma B.S., The University of British Columbia, 2022 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Human Nutrition) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) April 2024 © Yuexi Ma, 2024 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the thesis entitled: Investigating the Role of SIRT1 in Epigenetic Effects of Dietary Phytoestrogens in Human Mammary Epithelial Cells submitted by Yuexi Ma in partial fulfilment of the requirements for the degree of Master of Science in Human Nutrition Examining Committee: Dr. Barbara Stefanska, Associate Professor, Human Nutrition, UBC Supervisor Dr. Rajavel Elango, Associate Professor, Human Nutrition, UBC Supervisory Committee Member Dr. Tianxi Yang, Assistant Professor, Food Science, UBC Supervisory Committee Member Dr. David Kitts, Associate Dean, Food Science, UBC Additional Examiner iii Abstract Dietary factors, like polyphenols naturally occurring in plants, exert influences on human health via epigenetic mechanisms that alter gene expression without changing DNA sequence. We have previously performed genome-wide DNA methylation and expression analyses in human mammary epithelial cells and healthy rats’ livers, respectively, which were exposed to berry polyphenols with estrogenic activity (i.e., phytoestrogens). Using these datasets, we identified hypermethylated and/or downregulated genes enriched with functional categories that disrupt homeostasis and health maintenance, and promote aging, e.g., by limiting DNA break repair (RNF169) or promoting ribosomal biogenesis (rDNA). Existing evidence suggests that DNA methylation may be governed by chromatin regulatory proteins such as SIRT1 deacetylase. SIRT1 may inte…
has type: Thesis/Dissertation
date issued: 2024-05
is shown at: 10.14288/1.0441410
language: eng
degree discipline: Human Nutrition
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Stefanska, Barbara
type: Text
identifier URI: http://hdl.handle.net/2429/87884