In this project, Michael Piper and colleagues plan to analyze how H3K36 methylation impacts neural stem cell development and subsequent brain function, using transgenic mouse models lacking the enzymes required to add this epigenetic mark. Moreover, his team’s transcriptomic and epigenomic profiling will enable them to identify ‘points of convergence’ downstream of this mark, which they plan to validate using in vitro paradigms that include agonists and antagonists specific for these factors.

Piper’s studies are expected to have a significant impact on autism spectrum disorder (ASD) research in several ways. First, they are expected to provide global insight into how regulation of the chromatin landscape controls brain development and function during normal development as well as in disease (e.g., brain overgrowth). Second, they are anticipated to provide guidance for biomarker development, as epigenetic signatures offer a tractable target. Third, they are anticipated to lay the groundwork for using these points of epigenetic convergence as potential drug targets. Finally, the tools and processes that they aim to pioneer in their efforts to understand the epigenetic regulation of neural stem cell biology can be readily applied to other epigenetic genes implicated in ASD.