SMARCA4 is a haploinsufficient B cell lymphoma tumor suppressor that fine-tunes centrocyte cell fate decisions.

SMARCA4 encodes one of two mutually exclusive ATPase subunits in the BRG/BRM associated factor (BAF) complex that is recruited by transcription factors (TFs) to drive chromatin accessibility and transcriptional activation. SMARCA4 is among the most recurrently mutated genes in human cancer, including ∼30% of germinal center (GC)-derived Burkitt lymphomas. In mice, GC-specific Smarca4 haploinsufficiency cooperated with MYC over-expression to drive lymphomagenesis. Furthermore, monoallelic Smarca4 deletion drove GC hyperplasia with centroblast polarization via significantly increased rates of centrocyte recycling to the dark zone. Mechanistically, Smarca4 loss reduced the activity of TFs that are activated in centrocytes to drive GC-exit, including SPI1 (PU.1), IRF family, and NF-κB. Loss of activity for these factors phenocopied aberrant BCL6 activity within murine centrocytes and human Burkitt lymphoma cells. SMARCA4 therefore facilitates chromatin accessibility for TFs that shape centrocyte trajectories, and loss of fine-control of these programs biases toward centroblast cell-fate, GC hyperplasia and lymphoma.

Unsupported Micellar Palladium Nanoparticles for Biphasic Hydrogenation and Isomerization of Hydrophobic Allylic Alcohols in Water.

This article presents the evaluation of water-soluble palladium nanoparticles with hydrophobic active sites that are ideal for the biphasic colloidal catalysis of water-insoluble organic substrates in aqueous solution. Palladium nanoparticles stabilized with ω-carboxylate-functionalized alkanethiolate are first synthesized using ω-carboxylate-S-alkylthiosulfate as their ligand precursor. The biphasic catalysis is carried out for the reaction of hydrophobic allylic alcohols without using any additional mixing solvent or surfactant, which results in the complete consumption of substrates under the atmospheric pressure of H2 gas and at room temperature in less than 24 h. Systematic investigations on the influence of pH and substrate size are also performed to examine the utility of these thiolate-capped palladium nanoparticles as structurally stable and water-soluble micellar catalysts for the biphasic reaction.