(558) Epigenetic modifiers are altered with increased levels of polycyclic aromatic hydrocarbons (PAHs)

We have previously reported that increased placental levels of the ubiquitous PAH benzo[a]pyrene (BaP) is significantly associated with preterm birth (PTB). Furthermore, we have shown that increased levels of placental BaP are positively correlated with histone methylation, and acetylation. These epigenetic modifications can contribute to alterations in placental gene expression.  In this study we aimed to determine if the enzymes responsible for establishment and maintenance of these modifications were altered in association with BaP levels.

Study Design:

Protein extracts were derived from 77 placentae samples and were utilized for Reverse Phase Protein Array analyses of 38 proteins involved in the post-translational modification of histones or chromatin remodeling. Data was normalized to total histone protein levels. Absolute levels of BaP were measured from the same samples using GC-MS. Pearson product moment correlation coefficients were determined using R Studio.

Results:

We have previously shown that trimethylation of histone H3 were significantly, positively correlated with absolute levels of BaP on lysine 4 of histone H3 (H3K4me3; 0.585, p = 0.003) and lysine 9 of histone H3 (H3K9me3; 0.532, p=0.009). Here we find that levels of two histone demethylases, LSD1 (-0.317, p=0.007) and JARID1A (-0.347, p=0.003), are negatively correlated with BaP levels. We further found that EZH2, a histone methyltransferase, is also negatively correlated with BaP levels (-0.265, p=0.025). 

Conclusion: Our data reveal alterations to the placental histone code and the histone modifying enzymes in association with environmental exposures. Specifically, increased levels of BaP alters the epigenomic profile of the placenta, with likely downstream effects on gene expression. Further studies of changes in DNA methylation and gene expression are necessary to understand the consequences of an altered epigenome.