Heparin increases chromatin accessibility by binding the trypsin-sensitive basic residues in histones.
Recent evidence indicates that chromatin accessibility to transcription factors is of regulatory significance. The polyanion heparin is known to increase chromatin accessibility to DNAase I and to stimulate both RNA and DNA synthesis. In the present study, chromatin structure and its modification by polyanions were examined by using trypsin and micrococcal nuclease as probes. Both heparin and poly(glutamic acid) were found to be equivalent to trypsin digestion of histones in their ability to increase nuclease accessibility in chromatin. However, no increase in nuclease accessibility was observed when trypsin-digested chromatin was further treated with heparin, indicating that polyanions and trypsin are not additive in their effects on chromatin accessibility. Moreover, sucrose-gradient analysis demonstrated that heparin binds tightly to intact nucleosomes but not to trypsin-digested nucleosomes. These data suggest that polyanions interact predominantly with the trypsin-sensitive lysine and arginine residues in histone H1 and the N-terminal segments of the core histones. The possible relevance of these results to the chromatin structure of actively transcribed regions is discussed.
D000818:Animals; D001120:Arginine / Q000378:metabolism; D002417:Cattle; D002499:Centrifugation, Density Gradient; D002843:Chromatin / Q000187:drug effects* / Q000378:metabolism; D004357:Drug Synergism; D006493:Heparin / Q000494:pharmacology*; D006657:Histones / Q000187:drug effects / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008836:Micrococcal Nuclease / Q000378:metabolism; D009707:Nucleosomes / Q000187:drug effects / Q000378:metabolism; D011099:Polyglutamic Acid / Q000494:pharmacology; D011485:Protein Binding; D012680:Sensitivity and Specificity; D013268:Stimulation, Chemical; D013552:Swine; D014357:Trypsin / Q000494:pharmacology*
D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D011099:Polyglutamic Acid; D006493:Heparin; D001120:Arginine; D008836:Micrococcal Nuclease; D014357:Trypsin; D008239:Lysine