Identification of master genes involved in liver key functions through transcriptomics and epigenomics of methyl donor deficiency in rat: relevance to nonalcoholic liver disease.
METHODS
Our study aims to investigate molecular events associated to methyl donor deficiency (MDD) by analyzing the transcriptome and the methylome of MDD rats in liver.


RESULTS
Twenty-one-day-old rats born to mothers fed either with a standard diet or a MDD diet during gestation and lactation were compared. From a total of 44 000 probes for 26 456 genes, we found two gene clusters in MDD rats whose expression levels had significant differences compared with controls: 3269 overexpressed (p < 0.0009) and 2841 underexpressed (p < 0.0004) genes. Modifications of DNA methylation were found in the promoter regions of 1032 genes out of 14 981 genes. Ontological analyses revealed that these genes are mainly involved in glucose and lipid metabolism, nervous system, coagulation, ER stress, and mitochondrial function.


CONCLUSIONS
Putative master genes exhibiting changes in both gene expression and DNA methylation are limited to 266 genes and are mainly involved in the renin-angiotensin system (n = 3), mitochondrion metabolism (n = 18), and phospholipid homeostasis (n = 3). Most of these master genes participate in nonalcoholic fatty liver disease. The adverse effects of MDD on the metabolic process indicate the beneficial impact of folate and vitamin B12, especially during the perinatal period.
Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Médecine, Vandœuvre-lès-Nancy, France.
Gaili
G
Chen
Julien
J
Broséus
Sébastien
S
Hergalant
Audrey
A
Donnart
Catherine
C
Chevalier
Francisco
F
Bolaños-Jiménez
Jean-Louis
JL
Guéant
Rémi
R
Houlgatte
D000818:Animals; D019295:Computational Biology; D019175:DNA Methylation; D004032:Diet / Q000662:veterinary; D057890:Epigenomics; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000494:pharmacology; D015870:Gene Expression; D007774:Lactation; D050356:Lipid Metabolism; D008099:Liver / Q000502:physiology*; D008107:Liver Diseases / Q000235:genetics*; D039382:Maternal Nutritional Physiological Phenomena; D018743:Perinatal Care; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D059467:Transcriptome; D014805:Vitamin B 12 / Q000097:blood / Q000494:pharmacology
D005492:Folic Acid; D014805:Vitamin B 12
Fetal programing; Methyl donor deficiency; Methylome; NAFLD; Transcriptome