Nucleosomes Bind to Cell Surface Proteoglycans*
- From the Section on Clinical Pharmacology, Imperial College School of Medicine, Hammersmith Hospital, DuCane Road, London W12 0NN, United Kingdom
Abstract
Material on the surface of activated T-cells was displaced following incubation with a sulfated polysaccharide, dextrin 2-sulfate (D2S), and purified by anion-exchange chromatography. This revealed a complex comprising histones H2A, H2B, H3, and H4 and DNA fragmented into 180-base pair units characteristic of mono-, di-, tri, and polynucleosomes, a pattern of fragmentation similar to that found in apoptotic cells. An antibody raised against the purified nucleosome preparation bound to the plasma membrane of activated T-cells confirming the surface location of nucleosomes. The interaction of sulfated polysaccharides with nucleosomes was investigated using a biotinylated derivative of D2S. It was found that sulfated polysaccharides bound to nucleosomes via the N termini of histones, especially H2A and H2B. Treatment of T-cells with either heparinase or heparitinase abolished nucleosome binding to plasma membranes. This suggests that nucleosomes are anchored to the surface of T-cells by heparan sulfate proteoglycans through an ionic interaction with the basic N-terminal residues in the histones. Furthermore, nucleosomes bound to the cell surface in this manner are then able to bind other sulfated polysaccharides, such as D2S, heparin, or dextran sulfate, through unoccupied histone N termini forming a complex comprising cell surface heparan sulfate proteoglycans, nucleosomes, and sulfated polysaccharides.
Footnotes
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↵* This work was funded by ML Laboratories, Liverpool, UK.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ To whom correspondence should be addressed: Section on Clinical Pharmacology, Imperial College School of Medicine, Hammersmith Hospital, DuCane Rd., London W12 0NN, United Kingdom. Tel.: 44 181 383 2043; Fax: 44 181 383 2066; E-mail: kwatson@rpms.ac.uk.
- Abbreviations:
- SLE
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systemic lupus erythematosus
- D2S
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dextrin 2-sulfate
- HSPG
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heparan sulfate proteoglycans
- PBS
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phosphate-buffered saline
- PAGE
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polyacrylamide gel electrophoresis
- BSA
-
bovine serum albumin
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- Received April 26, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
