RGD Reference Report - Neonatal exposure to estradiol/bisphenol A alters promoter methylation and expression of Nsbp1 and Hpcal1 genes and transcriptional programs of Dnmt3a/b and Mbd2/4 in the rat prostate gland throughout life. - Rat Genome Database

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Neonatal exposure to estradiol/bisphenol A alters promoter methylation and expression of Nsbp1 and Hpcal1 genes and transcriptional programs of Dnmt3a/b and Mbd2/4 in the rat prostate gland throughout life.

Authors: Tang, WY  Morey, LM  Cheung, YY  Birch, L  Prins, GS  Ho, SM 
Citation: Tang WY, etal., Endocrinology. 2012 Jan;153(1):42-55. doi: 10.1210/en.2011-1308. Epub 2011 Nov 22.
RGD ID: 9588666
Pubmed: PMID:22109888   (View Abstract at PubMed)
PMCID: PMC3249669   (View Article at PubMed Central)
DOI: DOI:10.1210/en.2011-1308   (Journal Full-text)

Evidence supporting an early origin of prostate cancer is growing. We demonstrated previously that brief exposure of neonatal rats to estradiol or bisphenol A elevated their risk of developing precancerous lesions in the prostate upon androgen-supported treatment with estradiol as adults. Epigenetic reprogramming may be a mechanism underlying this inductive event in early life, because we observed overexpression of phosphodiesterase 4D variant 4 (Pde4d4) through induction of hypomethylation of its promoter. This epigenetic mark was invisible in early life (postnatal d 10), becoming apparent only after sexual maturation. Here, we asked whether other estrogen-reprogrammable epigenetic marks have similar or different patterns in gene methylation changes throughout life. We found that hypomethylation of the promoter of nucleosome binding protein-1 (Nsbp1), unlike Pde4d4, is an early and permanent epigenetic mark of neonatal exposure to estradiol/bisphenol A that persists throughout life, unaffected by events during adulthood. In contrast, hippocalcin-like 1 (Hpcal1) is a highly plastic epigenetic mark whose hypermethylation depends on both type of early-life exposure and adult-life events. Four of the eight genes involved in DNA methylation/demethylation showed early and persistent overexpression that was not a function of DNA methylation at their promoters, including genes encoding de novo DNA methyltransferases (Dnmt3a/b) and methyl-CpG binding domain proteins (Mbd2/4) that have demethylating activities. Their lifelong aberrant expression implicates them in early-life reprogramming and prostate carcinogenesis during adulthood. We speculate that the distinctly different fate of early-life epigenetic marks during adulthood reflects the complex nature of lifelong editing of early-life epigenetic reprogramming.




Biological Process
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Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Mbd1Ratresponse to bisphenol A  IEP  RGD 
Mbd2Ratresponse to bisphenol A  IEP  RGD 
Mbd3Ratresponse to bisphenol A  IEP  RGD 
Mecp2Ratresponse to bisphenol A  IEP  RGD 
Mbd1Ratresponse to estradiol  IEP  RGD 
Mbd2Ratresponse to estradiol  IEP  RGD 
Mbd3Ratresponse to estradiol  IEP  RGD 
Mbd4Ratresponse to estradiol  IEP  RGD 
Mecp2Ratresponse to estradiol  IEP  RGD 
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Genes (Rattus norvegicus)
Mbd1  (methyl-CpG binding domain protein 1) Mbd2  (methyl-CpG binding domain protein 2) Mbd3  (methyl-CpG binding domain protein 3)
Mbd4  (methyl-CpG binding domain 4 DNA glycosylase) Mecp2  (methyl CpG binding protein 2)