GSE123084
A chemical probe for Tudor domain protein SPIN1 to investigate chromatin functions
Lysine and arginine methylation are amongst the most frequent modifications on unstructured histone tails and in combination with other modifications provide the basis for a combinatorial 'chromatin or histone code'. Recognition of modified histone residues is accomplished in a specific manner by 'reader' domains that recognize chromatin modifications allowing to associate with specific effector complexes mediating chromatin functions. The methyl-lysine and methyl-arginine reader domain protein SPINDLIN1 (SPIN1) belongs to a family of 5 human genes, and has been identified as a putative oncogene and  transcriptional co-activator containing three Tudor domains, able to mediate chromatin binding. Here we report on the discovery of the potent and selective bivalent Tudor domain inhibitor VinSPINIn, which simultaneously engages Tudor domains 1 and 2 and effectively competes with chromatin binding. Inhibitor, chemoproteomic and knockdown studies in squamous cell carcinoma suggest an un-anticipated complexity of SPIN isoform mediated interactions in regulating cellular phenotypes. Overall design: Triplicates for 2 compounds, 1 siRNA, DMSO and scrambled siRNA control at 2 time points are examined by RNA-Seq