
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Ноя. 2, 2024
Abstract Linkage-specific ubiquitin chains dictate the functional outcome of numerous critical ubiquitin-dependent signaling processes. However, functions and targets several poly-ubiquitin topologies remain poorly defined due to a paucity tools for their specific detection manipulation. To remedy this knowledge gap, we applied cell-based replacement strategy enabling targeted conditional abrogation each seven lysine-based chain types in human cells profile system-wide impacts disabling formation individual types. Focusing on K29-linked ubiquitylation, reveal strong association linkage type with chromatin-associated proteins show that H3K9me3 methyltransferase SUV39H1 is prominent cellular target modification. We demonstrate ubiquitylation essential proteasomal degradation despite its extensive modification by K48-linked catalyzed reversed TRIP12 TRABID, respectively. Preventing ubiquitylation-mediated control stability deregulates landscape, but not other histone marks. Collectively, our cell line panel datasets provide valuable resources illuminating linkage-specific establish key role epigenome integrity.
Язык: Английский