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Publication : Obesity, rather than diet, drives epigenomic alterations in colonic epithelium resembling cancer progression.

First Author  Li R Year  2014
Journal  Cell Metab Volume  19
Issue  4 Pages  702-11
PubMed ID  24703701 Mgi Jnum  J:213146
Mgi Id  MGI:5582973 Doi  10.1016/j.cmet.2014.03.012
Citation  Li R, et al. (2014) Obesity, rather than diet, drives epigenomic alterations in colonic epithelium resembling cancer progression. Cell Metab 19(4):702-11
abstractText  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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