Chaperone proteins bind to histones and escort them through the cell. In the nucleus, they remove and deposit histones during transcription, replication, and repair of the DNA. We study how chaperones bind to histones both to stabilize them and to deposit histones into nucleosomes. We propose that the major clue to chaperone molecular mechanisms lies in their only conserved feature: their acidic-stretches embedded in intrinsically disordered regions (IDRs). In this "Fly Fishing for Histones" model (here), the IDRs are baited to catch and release histone proteins. Our studies use novel structural and biological approaches to target these chaperone IDRs and their post-translational modifications, particularly the unusual glutamylation of the acidic IDRs. Our studies, ongoing in both Xenopus laevis cell-free extracts and in AML cancer cells, are exploring the critical role of chaperone glutamylation in regulation of these essential biological processes.