title: Methyltransferases prefer monomer over core-trimmed nucleosomes as in vitro substrates.
abstract: Epigenetics is an area of increasing interest for drug discovery, driving the need for assays that use nucleosome substrates. Our studies showed that SUV39H1, a histone lysine methyltransferase, and Dnmt3b/Dnmt3L, a DNA methyltransferase, both exhibited approximately five times more activity on monomer nucleosomes than on DNA-core-trimmed nucleosomes in a scintillation proximity assay (SPA). The methyltransferases recognize and have a preference for nucleosomes with longer DNA strands. Our findings suggest that the use of monomer nucleosomes as substrates using SPA technology could lead to more robust screening assays and potentially more specific small molecule inhibitors of epigenetic enzymes.
authors: Department of Biological Reagents and Assay Development, GlaxoSmithKline, Collegeville, PA 19426, USA.
authors: Yong
authors: Y
authors: Jiang
authors: Jessica L
authors: JL
authors: Schneck
authors: Maggie
authors: M
authors: Grimes
authors: Amy N
authors: AN
authors: Taylor
authors: Wangfang
authors: W
authors: Hou
authors: Sara H
authors: SH
authors: Thrall
authors: Sharon M
authors: SM
authors: Sweitzer
mesh_terms: D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D057890:Epigenomics; D006367:HeLa Cells; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006801:Humans; D009707:Nucleosomes / Q000378:metabolism*; D013379:Substrate Specificity; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D009707:Nucleosomes; D000097584:DNA Methyltransferase 3B