Obesity, Rather Than Diet, Drives Epigenomic Alterations in Colonic Epithelium Resembling Cancer Progression

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2014 Apr 8

PMID 24703701

Citations 33

Authors

Ruifang Li

Sara A Grimm

Kaliopi Chrysovergis

Justin Kosak

Xingya Wang

Ying Du

Adam Burkholder

Kyathanahalli Janardhan

Deepak Mav

Ruchir Shah

Thomas E Eling

Paul A Wade

Affiliations

Soon will be listed here.

Abstract

While obesity represents one of several risk factors for colorectal cancer in humans, the mechanistic underpinnings of this association remain unresolved. Environmental stimuli, including diet, can alter the epigenetic landscape of DNA cis-regulatory elements affecting gene expression and phenotype. Here, we explored the impact of diet and obesity on gene expression and the enhancer landscape in murine colonic epithelium. Obesity led to the accumulation of histone modifications associated with active enhancers at genomic loci downstream of signaling pathways integral to the initiation and progression of colon cancer. Meanwhile, colon-specific enhancers lost the same histone mark, poising cells for loss of differentiation. These alterations reflect a transcriptional program with many features shared with the program driving colon cancer progression. The interrogation of enhancer alterations by diet in colonic epithelium provides insights into the biology underlying high-fat diet and obesity as risk factors for colon cancer.

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