Abstract:

More than half of human DNA is classified as repetitive either in the sense that there are many copies of the sequence interspersed in the genome, the nucleotide sequence is itself repetitive, or both. Such elements can mobilise or expand and tight control of repeat transcription is fundamental to preserving genome stability. The HUSH complex and its effector MORC2 have emerged as critical epigenetic regulators of LINE-1 retrotransposons and other genomic repeats. In this talk I will describe our efforts to bridge biochemistry and structure with functional genomics to unpick the mechanisms of how the HUSH-MORC2 corepressor works. In particular I will describe (1) how MORC2 is recruited to repeats and regulates chromatin structure, (2) how HUSH-MORC2 works alongside DNA methylation to control repeats in the somatic cells of the developing brain, and (3) the relevance of these mechanisms in patients with severe neurodevelopmental disorders. 

By: Paula Amiet-West
Last updated: Wednesday, 10 July 2024