Program > Browse abstracts by author > Parham Andrea

Transposable elements (TEs) and endogenous retroviruses (ERVs) constitute nearly half of the mammalian genome. TE and ERV activation is critical for normal embryonic development but aberrant expression in later life can cause hemophilia, cystic fibrosis, infertility, metabolic disease, cancer, and neurodegenerative disease. After early development, most TEs and ERVs are fully “silenced” via DNA methylation and histone modifications. However, a subset of ERVs (e.g., certain intracisternal A-particles; IAPs) become variably methylated (VM-ERVs), escape normal silencing mechanisms, and influence neighboring gene expression in cis or trans, in a cell- or developmental/time-dependent manner. Recent in vitro studies indicate that N6-methyladenosine (m6A) marks on RNA can regulate gene expression co-transcriptionally or through m6A-methylated nascent RNA interactions with DNA. They showed that decreased RNA m6A levels promotes an open chromatin state and increases regulatory RNA expression (including ERVs). Whether these proposed mechanisms apply to VM-ERV activation/repression remains unknown, yet understanding the epigenetic to epitranscriptomic level of control in vivo might help explain the origins of some of the aforementioned diseases. The objective of this project is therefore to determine if RNA m6A marks are connected to VM-ERV DNA methylation and VM-ERV activation in vivo. This project will provide the first indication that m6A RNA marks regulate VM-ERV activity and VM-ERV DNA methylation state in vivo.