Maternal Exposure to High-Fat Diet Induces Long-Term Derepressive Chromatin Marks in the Heart.

Details

Serval ID
serval:BIB_71941CF51B80
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Maternal Exposure to High-Fat Diet Induces Long-Term Derepressive Chromatin Marks in the Heart.
Journal
Nutrients
Author(s)
Blin G., Liand M., Mauduit C., Chehade H., Benahmed M., Simeoni U., Siddeek B.
ISSN
2072-6643 (Electronic)
ISSN-L
2072-6643
Publication state
Published
Issued date
09/01/2020
Peer-reviewed
Oui
Volume
12
Number
1
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Heart diseases are a leading cause of death. While the link between early exposure to nutritional excess and heart disease risk is clear, the molecular mechanisms involved are poorly understood. In the developmental programming field, increasing evidence is pointing out the critical role of epigenetic mechanisms. Among them, polycomb repressive complex 2 (PRC2) and DNA methylation play a critical role in heart development and pathogenesis. In this context, we aimed at evaluating the role of these epigenetic marks in the long-term cardiac alterations induced by early dietary challenge. Using a model of rats exposed to maternal high-fat diet during gestation and lactation, we evaluated cardiac alterations at adulthood. Expression levels of PRC2 components, its histone marks di- and trimethylated histone H3 (H3K27me2/3), associated histone mark (ubiquitinated histone H2A, H2AK119ub1) and target genes were measured by Western blot. Global DNA methylation level and DNA methyl transferase 3B (DNMT3B) protein levels were measured. Maternal high-fat diet decreased H3K27me3, H2Ak119ub1 and DNA methylation levels, down-regulated the enhancer of zeste homolog 2 (EZH2), and DNMT3B expression. The levels of the target genes, isl lim homeobox 1 (Isl1), six homeobox 1 (Six1) and mads box transcription enhancer factor 2, polypeptide C (Mef2c), involved in cardiac pathogenesis were up regulated. Overall, our data suggest that the programming of cardiac alterations by maternal exposure to high-fat diet involves the derepression of pro-fibrotic and pro-hypertrophic genes through the induction of EZH2 and DNMT3B deficiency.
Keywords
DNA methylation, development, heart, high-fat diet, polycomb repressive complex
Pubmed
Open Access
Yes
Create date
17/01/2020 17:05
Last modification date
24/01/2020 7:26
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