Invited Speaker Australian Epigenetics Alliance Conference 2022

Mobile DNA shuffles the regulatory landscape and somatic genome of PV interneurons (#16)

Geoffrey Faulkner 1
  1. The University of Queensland, .., QLD, Australia

The instructions required to produce a mature neuron are encoded in our DNA. In most mammals, the genomic landscape is dominated by mobile DNA, or "jumping genes". This includes the retrotransposon LINE-1 (L1), which makes up ~20% of the mouse and human genomes. Over the past few years, long-read epigenome and transcriptome sequencing technologies developed by Oxford Nanopore Technologies (ONT) and Pacific Biosciences (PacBio) have transformed our ability to study the impact of L1 elements on gene regulation. Similarly, single-cell whole genome sequencing (scWGS) now allows us to identify L1 insertions arising in neuronal populations. In this talk, I will share our surprising results generated using these technologies, revealing that somatic L1 retrotransposition is specific to parvalbumin (PV) interneurons, apparently due to SOX6 expression in this lineage. Perhaps more importantly, L1 promoter DNA demethylation as a precursor to L1 jumping also enables alternative transcription of key PV neuron genes, such as Caps2. This study therefore discovers the incorporation of mobile DNA regulatory elements into the transcriptional program governing PV neuron development