Structure-function relationship of ASH1L and histone H3K36 and H3K4 methylation.

The histone H3K36-specific methyltransferase ASH1L plays a critical role in development and is frequently dysregulated in human diseases, particularly cancer. Here, we report on the biological functions of the C-terminal region of ASH1L encompassing a bromodomain (ASH1L), a plant homeodomain (ASH1L) finger, and a bromo-adjacent homology (ASH1L) domain, structurally characterize these domains, describe their mechanisms of action, and explore functional crosstalk between them. We find that ASH1L recognizes H3K4me2/3, whereas the neighboring ASH1L and ASH1L have DNA binding activities.

Deuterium labeling enables proteome wide turnover kinetics analysis in cell culture.

The half-life of proteins is tightly regulated and underlies many cellular processes. It remains unclear the extent to which proteins are dynamically synthesized and degraded in different cell types and cell states. We introduce an improved DO labeling workflow and apply it to examine the landscape of protein turnover in pluripotent and differentiating human induced pluripotent stem cells (hiPSC).