Epigenetic effects of a PCB exposure during eartly development in the rat

Introduction: the epigenetic control of gene transcription is fundamental in establishing and maintaining cell identity during embryogenesis. Deregulation of epigenetic mechanisms may be responsible for incorrect transcription patterns during critical periods of development, resulting in stable modifications of many key physiological processes. The two main epigenetic controls are: 1- the methylation status of cytosines within CpG islands located in the promoter region of many genes, which modulates transcription factor binding to DNA recognition sites; 2- post-translational acetylation or methylation of lysines (K) in the histone N-terminal region, which influence chromatin packaging. Prenatal exposure to the pollutants PCBs (polychlorinated biphenyls) through placental transfer and lactation modifies the transcription pattern of many proteins; it is unclear whether this action is mediated only through receptor-mediated mechanisms or whether alterations of the epigenetic mechanisms are also involved. Aim: to evaluate whether prenatal administration of four PCB indicators (138, 153, 180, 126) is able to influence the epigenetic signature in different tissues of exposed animals. Results: PCB exposure reduces the K4 trimethylation on histone 3 and the K16 acetylation on histone 4 (hallmarks of transcription activation), causing a generalized inhibition of gene transcription; interestingly, the PCB influence on this mechanism seem to be dimorphic. In contrast, the methylation status of CpG islands does not seem to be affected by PCBs. Conclusion: exposure to PCBs might interfere with many developmental processes through epigenetic alterations of the chromatin packaging.