HALOS webinar series: Synchrotron light and epigenomics combine to reveal mechanisms of viral chromatin regulation by the Human Silencing Hub (HUSH) complex
Speaker: Dr. Christopher Douse
Department of Experimental Medical Science, Lund University
About: The human genome is evolving under constant threat of colonization by infectious retroviruses and transposons. The Human Silencing Hub (HUSH) complex has recently emerged as a central player in the repression of such mobile genetic elements. HUSH regulates deposition of the epigenetic mark H3K9me3 over its targets, and recruits MORC2, an ATPase reported to have chromatin remodelling activity. Patient mutations in MORC2 have been shown to cause severe neuro-developmental disorders. These recent discoveries raise several mechanistic questions. How do HUSH subunits assemble on chromatin? How do HUSH and MORC2 repress their targets? And how does MORC2 mutation misregulate its function to cause human disease? To address these questions we have undertaken a systematic, multi-scale analysis of the structural, biochemical and functional properties of MORC2 and the core HUSH scaffold, TASOR. I will describe our latest model for how this critical protein machinery works to defend the human genome.