title: Pentraxin-chromatin interactions: serum amyloid P component specifically displaces H1-type histones and solubilizes native long chromatin.
abstract: Pure serum amyloid P component (SAP) and native long chromatin, mixed together at wt/wt ratios between 1:1 and 1:2 in the presence of physiological concentrations of NaCl and calcium, both remained in solution, whereas each alone precipitates rapidly under these conditions. This solubilization accompanies the binding of SAP to chromatin and the displacement of H1-type histones, which are essential for condensation and higher order folding of chromatin. Such binding of SAP to chromatin is remarkable since displacement of H1 and H5 by salt alone requires approximately 0.5 M NaCl. SAP also bound to nucleosome core particles forming soluble complexes with an apparent stoichiometry of 1:2, a result that is compatible with attachment of SAP at the nucleosome dyad, the site of H1 in intact chromatin. SAP thus undergoes a specific, avid interaction with chromatin that promotes its solubilization and may thereby contribute to the physiological handling of chromatin released from cells in vivo. In contrast, C-reactive protein (CRP) did not bind significantly to either chromatin or to core particles at physiological ionic strength. Incubation of chromatin with either normal serum, or acute phase human serum containing raised levels of CRP, did not induce complement activation regardless of the presence of added SAP or CRP, nor was any cleavage of DNA observed.
authors.affiliation: Department of Medicine, Royal Postgraduate Medical School, London, United Kingdom.
authors.forename: P J
authors.initials: PJ
authors.lastname: Butler
authors.forename: G A
authors.initials: GA
authors.lastname: Tennent
authors.forename: M B
authors.initials: MB
authors.lastname: Pepys
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism / Q000502:physiology; D002499:Centrifugation, Density Gradient; D002645:Chickens; D002843:Chromatin / Q000378:metabolism*; D003167:Complement Activation; D004247:DNA / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006657:Histones / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D009994:Osmolar Concentration; D000683:Serum Amyloid P-Component / Q000378:metabolism* / Q000502:physiology; D012995:Solubility
chemical_list: D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D000683:Serum Amyloid P-Component; D002097:C-Reactive Protein; D004247:DNA