title: A gestational low-protein diet represses p21(WAF1/Cip1) expression in the mammary gland of offspring rats through promoter histone modifications.
abstract: Maternal exposure to environmental agents throughout pregnancy may change certain metabolic processes during the offspring's mammary gland development and alter the epigenome. This may predispose the offspring to breast cancer later in life. The purpose of the present study was to examine the effect of maternal protein restriction on the regulation of cyclin-dependent kinase inhibitor 1 (p21) gene expression in the mammary gland of rat offspring. Timed-mated Sprague-Dawley rats were fed one of the two isoenergetic diets, control (C, 18 % casein) or low protein (LP, 9 % casein), during gestation. Compared with the C group, LP offspring showed a decrease of p21 in the mammary gland at both the mRNA and protein levels. Chromatin immunoprecipitation assay demonstrated that the down-regulation of p21 transcription in LP offspring was associated with reduced acetylation of histone H3 and dimethylation of H3K4 within the p21 promoter region, but was not associated with acetylation of histone H4 or histone methylation. DNA methylation analysis using bisulphite sequencing did not detect differences in methylation at the p21 promoter between the offspring of the C and LP groups. We conclude that maternal protein restriction inhibits p21 gene expression in the mammary gland of offspring through histone modifications at the promoter region of the p21 gene.
authors.affiliation: Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, 461 Bevier Hall, MC 182, 905 S Goodwin Avenue, Urbana, IL 61801, USA.
authors.forename: Shasha
authors.initials: S
authors.lastname: Zheng
authors.forename: Michelle
authors.initials: M
authors.lastname: Rollet
authors.forename: Kefeng
authors.initials: K
authors.lastname: Yang
authors.forename: Yuan-Xiang
authors.initials: YX
authors.lastname: Pan
mesh_terms: D000107:Acetylation; D000818:Animals; D001943:Breast Neoplasms / Q000209:etiology; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018753:Diet, Protein-Restricted / Q000009:adverse effects; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D005260:Female; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000254:growth & development / Q000378:metabolism*; D039382:Maternal Nutritional Physiological Phenomena; D008745:Methylation; D009928:Organ Specificity; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C493958:Cdkn1a protein, rat; D002843:Chromatin; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D006657:Histones; D012333:RNA, Messenger