Persistent Hypomethylation in the Promoter of Nucleosomal Binding Protein 1 (Nsbp1) Correlates with Overexpression of Nsbp1 in Mouse Uteri Neonatally Exposed to Diethylstilbestrol or Genistein

• DOI: 10.1210/en.2008-0682
• Publication Date: 2008-08-01T01:10:06Z
• Authors: Wan-Yee Tang; Retha Newbold; Katerina Mardilovich; Wendy Jefferson; Robert Y. S. Cheng; Mario Medvedovic; Shuk-Mei Ho
• Keywords: Male; Reverse Transcriptase Polymerase Chain Reaction; Ovariectomy; Uterus; Gene Expression; Sequence Analysis, DNA; DNA Methylation; Genistein; Mice; Animals, Newborn; Animals; Cluster Analysis; HMGN Proteins; Female; Promoter Regions, Genetic; Diethylstilbestrol

Neonatal exposure of CD-1 mice to diethylstilbestrol (DES) or genistein (GEN) induces uterine adenocarcinoma in aging animals. Uterine carcinogenesis this model is ovarian dependent because its evolution blocked by prepubertal ovariectomy. This study seeks discover novel genes whose expression altered such early endocrine disruption via an epigenetic mechanism. were treated with 1 1000 μg/kg DES, 50 mg/kg GEN, oil (control) on d 1–5. One group was killed before puberty 19. Others ovariectomized left intact, and at 6 18 months age. Methylation-sensitive restriction fingerprinting performed identify differentially methylated sequences associated neonatal DES/GEN. Among 14 candidates, nucleosomal binding protein (Nsbp1), the gene for a nucleosome-core-particle protein, selected further central role chromatin remodeling. In uteri immature control mice, Nsbp1 promoter CpG island (CGI) minimally methylated. Once reached puberty, CGI became hypermethylated, declined further. contrast, DES/GEN-treated stayed anomalously hypomethylated, exhibited persistent overexpression throughout life. However, if remained moderately methylated, subdued except DES. Thus, life reprogramming DES/GEN appears be mediated mechanism that interacts hormones adulthood.