title: GR and HMGB1 interact only within chromatin and influence each other's residence time.
abstract: Most nuclear proteins reside on a specific chromatin site only for seconds or less. The hit-and-run model of transcriptional control maintains that transcription complexes are assembled in a stochastic fashion from freely diffusible proteins; this contrasts to models involving stepwise assembly of stable holo complexes. However, the chances of forming a productive complex improve if the binding of one factor promotes the binding of its interactors. We prove here that in living cells, the glucocorticoid receptor and HMGB1 interact only within chromatin and not in the nucleoplasm and decrease each other's mobility. Thus, the formation of a GR-HMGB1-chromatin complex is more likely than one would expect from independent binding to chromatin of GR and HMGB1. Remarkably, this complex is potentially stable, and its disassembly is effected by active, ATP-consuming processes. We propose that kinetic cooperativity among transcription factors in chromatin binding may be a common feature in transcription and DNA transactions.
authors.affiliation: San Raffaele Research Institute, Via Olgettina 58, 20132 Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Agresti
authors.forename: Paola
authors.initials: P
authors.lastname: Scaffidi
authors.forename: Alberto
authors.initials: A
authors.lastname: Riva
authors.forename: Valeria R
authors.initials: VR
authors.lastname: Caiolfa
authors.forename: Marco E
authors.initials: ME
authors.lastname: Bianchi
mesh_terms: D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D017931:DNA Primers; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D018613:Microscopy, Confocal; D016366:Open Reading Frames; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D002843:Chromatin; D017931:DNA Primers; D024243:HMGB1 Protein; D011965:Receptors, Glucocorticoid; D011993:Recombinant Fusion Proteins