title: Different effects of histone H1 on de novo DNA methylation in vitro depend on both the DNA base composition and the DNA methyltransferase.
abstract: We have characterized the inhibition exerted by histone H1 on the activity of human placenta DNA (cytosine-5-)-methyltransferase. Our experiments demonstrate that the extent of inhibition depends on the DNA base composition, AT-rich substrates being more severely affected than GC-rich substrates and CpG-rich islands. With bacterial SssI methylase, the effect is completely reversed since its activity on AT-rich substrates undergoes a 4-5-fold stimulation upon the addition of H1. Poly(L-lysine) mimicks H1 effects, suggesting an essential role of lysine residues in both the inhibitory and stimulatory effects of H1. By comparison of the different behaviors of the two enzymes, the inhibitory effect over the eukaryotic enzyme might be accounted for by hypothesizing a competition between minor groove-binding motifs (SPKK-like) present in placenta methylase as well as in histone H1.
authors.affiliation: Department of Biochemical Sciences A. Rossi Fanelli, University of Rome La Sapienza, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Carotti
authors.forename: S
authors.initials: S
authors.lastname: Funiciello
authors.forename: P
authors.initials: P
authors.lastname: Lavia
authors.forename: P
authors.initials: P
authors.lastname: Caiafa
authors.forename: R
authors.initials: R
authors.lastname: Strom
mesh_terms: D001482:Base Composition; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D015257:DNA-Cytosine Methylases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006657:Histones / Q000494:pharmacology*; D006801:Humans; D008745:Methylation / Q000187:drug effects; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology; D010920:Placenta / Q000201:enzymology; D011089:Polydeoxyribonucleotides / Q000378:metabolism; D011107:Polylysine / Q000494:pharmacology
chemical_list: D006657:Histones; D010455:Peptides; D011089:Polydeoxyribonucleotides; D011107:Polylysine; C015462:polyarginine; C019530:poly(dC-dG); D004247:DNA; C081573:DNA modification methylase SssI; D015257:DNA-Cytosine Methylases