title: Alteration in methylation pattern of GATA-4 promoter region in vitamin A-deficient offspring's heart.
abstract: Epigenetics might explain correlations between lifestyle and risk of disease. Maternal diet has been shown to dynamically alter epigenetic regulation, including affecting DNA methylation status. This study was designed to test the hypothesis that GATA-4 gene methylation would lead to congenital heart defects in vitamin A-deficient offspring. Ten weaning female rats (VAN group) were fed with a diet which contents 4 IU vitamin A/g diet, while 20 rats (VAD group) were maintained on a diet without vitamin A. After 10 weeks of feeding, all the female rats were mated with normal male rats. The VAN group and a portion of VAD group rats were still given the same diet as before mating, while the rest of the rats from the VAD group (VADS group) were transferred to a diet with enough added vitamin A (10 IU/g diet) for the pregnancy cycle. The embryo hearts were dissected out at embryonic day 13.5 (E13.5) for observation of cardiac development, GATA-4 gene methylation status and the expression of DNA methyltransferases (DNMTs). Embryos from vitamin A-deficient group exhibited a high incidence of cardiac defects. High methylation was present in the CpG loci of GATA-4 gene with a low expression of GATA-4 mRNA from vitamin A-deficient group embryos. Moreover, up-regulation of DNMT1 and down-regulation of DNMT3a and DNMT3b expression were found in this group embryo. These findings show that aberrant methylation is one of key mechanisms to heart defects in vitamin A-deficient offspring. DNMTs play a critical role in this process.
authors: Department of Clinical Nutrition, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
authors: Yi
authors: Y
authors: Feng
authors: Ling-Zi
authors: LZ
authors: Zhao
authors: Li
authors: L
authors: Hong
authors: Chuan
authors: C
authors: Shan
authors: Wen
authors: W
authors: Shi
authors: Wei
authors: W
authors: Cai
mesh_terms: D000818:Animals; D001483:Base Sequence; D018899:CpG Islands; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation; D017931:DNA Primers; D015536:Down-Regulation; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics*; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D014802:Vitamin A Deficiency / Q000235:genetics*
chemical_list: D017931:DNA Primers; D050991:GATA4 Transcription Factor; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619382:Dnmt1 protein, rat