Linking chromatin acylation mark-defined proteome and genome in living cells.

A generalizable strategy with programmable site specificity for in situ profiling of histone modifications on unperturbed chromatin remains highly desirable but challenging. We herein developed a single-site-resolved multi-omics (SiTomics) strategy for systematic mapping of dynamic modifications and subsequent profiling of chromatinized proteome and genome defined by specific chromatin acylations in living cells. By leveraging the genetic code expansion strategy, our SiTomics toolkit revealed distinct crotonylation (e.

The transcriptional coactivator RUVBL2 regulates Pol II clustering with diverse transcription factors.

RNA polymerase II (Pol II) apparatuses are compartmentalized into transcriptional clusters. Whether protein factors control these clusters remains unknown. In this study, we find that the ATPase-associated with diverse cellular activities (AAA + ) ATPase RUVBL2 co-occupies promoters with Pol II and various transcription factors.

Photocatalytic Chemical Crosslinking for Profiling RNA-Protein Interactions in Living Cells.

The dynamic interactions between RNAs and proteins play crucial roles in regulating diverse cellular processes. Proteome-wide characterization of these interactions in their native cellular context remains desirable but challenging. Herein, we developed a photocatalytic crosslinking (PhotoCAX) strategy coupled with mass spectrometry (PhotoCAX-MS) and RNA sequencing (PhotoCAX-seq) for the study of the composition and dynamics of protein-RNA interactions.

Genetically Encoded Photoaffinity Histone Marks.

Posttranslational modifications (PTMs) of lysine are crucial histone marks that regulate diverse biological processes. The functional roles and regulation mechanism of many newly identified lysine PTMs, however, remain yet to be understood. Here we report a photoaffinity crotonyl lysine (Kcr) analogue that can be genetically and site-specifically incorporated into histone proteins.

Design, synthesis, and evaluation of indanone derivatives as acetylcholinesterase inhibitors and metal-chelating agents.

A series of novel indanone derivatives was designed, synthesised and evaluated as potential agents for Alzheimer's disease. Among them, compound 6a, with a piperidine group linked to indone by a two-carbon spacer, exhibited the most potent inhibitor activity, with an IC(50) of 0.0018 μM for AChE; the inhibitory activity of this compound was 14-fold more potent than that of donepezil.

Berberine derivatives, with substituted amino groups linked at the 9-position, as inhibitors of acetylcholinesterase/butyrylcholinesterase.

Berberine derivatives with substituted amino groups linked at the 9-position using different carbon spacers were designed, synthesized, and biologically evaluated as inhibitors of acetylcholinesterase. Compound 10b, with a cyclohexylamino group linked to berberine by a three carbon spacer, gave the most potent inhibitor activity with an IC(50) of 0.020 μM for AChE.