Tang, Wan-yee Morey, Lisa M. Cheung, Yuk Yin Birch, Lynn Prins, Gail S. Ho, Shuk-mei 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 RatProstate Gland Throughout Life 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. untagged 2013-11-22
    https://indigo.uic.edu/articles/journal_contribution/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_RatProstate_Gland_Throughout_Life/10760234